Inflammation (
LatinLatin is an Italic language originally spoken in Latium and Ancient Rome. Through the Roman conquest, Latin spread throughout the Mediterranean and a large part of Europe...
,
inflammatio, a setting on fire) is the complex biological response of
vascularThe blood vessels are the part of the circulatory system that transport blood throughout the body. There are three major types of blood vessels: the arteries, which carry the blood away from the heart, the capillaries, which enable the actual exchange of water and chemicals between the blood and...
tissues to harmful stimuli, such as
pathogenA pathogen , infectious agent, or germ, is a biological agent that causes disease or illness to its host....
s, damaged cells, or irritants. Inflammation is a protective attempt by the organism to remove the injurious stimuli as well as initiate the healing process for the tissue. Inflammation is not a synonym for
infectionAn infection is the detrimental colonization of a host organism by a foreign species. In an infection, the infecting organism seeks to utilize the host's resources to multiply, usually at the expense of the host. The infecting organism, or pathogen, interferes with the normal functioning of the...
. Even in cases where inflammation is caused by infection, the two are not synonymous: infection is caused by an exogenous pathogen, while inflammation is one of the responses of the organism to the pathogen.
In the absence of inflammation, wounds and infections would never heal and progressive destruction of the tissue would compromise the survival of the organism. However, chronic inflammation can also lead to a host of diseases, such as
hay feverHay Fever is a comic play written by Noël Coward in 1924 and first produced in 1925 with Marie Tempest as the first Judith Bliss.Laura Hope Crewes played the role in New York...
,
atherosclerosisAtherosclerosis is the condition in which an artery wall thickens as the result of a build-up of fatty materials such as cholesterol...
, and
rheumatoid arthritisRheumatoid arthritis is a chronic, systemic inflammatory disorder that may affect many tissues and organs, but principally attacks the joints producing an inflammatory synovitis that often progresses to destruction of the articular cartilage and ankylosis of the joints...
. It is for that reason that inflammation is normally closely regulated by the body.
Inflammation can be classified as either
acute or
chronic.
Acute inflammation is the initial response of the body to harmful stimuli and is achieved by the increased movement of
plasmaBlood plasma is the yellow liquid component of blood, in which the blood cells in whole blood would normally be suspended. It makes up about 55% of the total blood volume. It is mostly water and contains dissolved proteins, glucose, clotting factors, mineral ions, hormones and carbon dioxide...
and leukocytes from the blood into the injured tissues. A cascade of biochemical events propagates and matures the inflammatory response, involving the local vascular system, the
immune systemAn immune system is a system of biological structures and processes within an organism that protects against disease by identifying and killing pathogens and tumour cells. It detects a wide variety of agents, from viruses to parasitic worms, and needs to distinguish them from the organism's own...
, and various cells within the injured tissue. Prolonged inflammation, known as
chronic inflammation, leads to a progressive shift in the type of cells which are present at the site of inflammation and is characterized by simultaneous destruction and
healingHealing is the act or process of curing or of restoring to health. Assessed physically, healing is the process by which the cells in the body regenerate and repair to reduce the size of a damaged or necrotic area....
of the tissue from the inflammatory process.
Causes
- Burn
A burn is a type of injury that may be caused by heat, electricity, chemicals, light, radiation, or friction. Burns can be highly variable in terms of the tissue affected, the severity, and resultant complications. Muscle, bone, blood vessel, dermal and epidermal tissue can all be damaged with...
s
- Chemical irritant
Irritation or exacerbation, in biology and physiology, is a state of inflammation or painful reaction to allergy or cell-lining damage. A stimulus or agent which induces the state of irritation is an irritant...
s
- Frostbite
Frostbite-is a condition that results in body tissues is frozen. the next step is hyporterma. is the medical condition wherein localized damage is caused to skin and other tissues due to extreme cold....
- Toxin
A toxin is a poisonous substance produced by living cells or organisms ....
s
- Infection
An infection is the detrimental colonization of a host organism by a foreign species. In an infection, the infecting organism seeks to utilize the host's resources to multiply, usually at the expense of the host. The infecting organism, or pathogen, interferes with the normal functioning of the...
by pathogenA pathogen , infectious agent, or germ, is a biological agent that causes disease or illness to its host....
s
- Physical injury, blunt or penetrating
- Immune reactions due to hypersensitivity
Hypersensitivity refers to undesirable reactions produced by the normal immune system. Hypersensitivity reactions require a pre-sensitized state of the host. The four-group classification was expounded by P. H. G...
- Ionizing radiation
Ionizing radiation consists of subatomic particles or electromagnetic waves that are energetic enough to detach electrons from atoms or molecules, ionizing them. The occurrence of ionization depends on the energy of the impinging individual particles or waves, and not on their number...
- Foreign bodies, including splinters and dirt
Types
Comparison between acute and chronic inflammation:
| |
Acute |
Chronic |
| Causative agent |
Pathogens, injured tissues |
Persistent acute inflammation due to non-degradable pathogens, persistent foreign bodies, or autoimmune reactions |
| Major cells involved |
Neutrophils, mononuclear cells (monocytes, macrophages) |
Mononuclear cells (monocytes, macrophages, lymphocytes, plasma cells), fibroblasts |
| Primary mediators |
Vasoactive amines, eicosanoids |
IFN-γ and other cytokines, growth factors, reactive oxygen species, hydrolytic enzymes |
| Onset |
Immediate |
Delayed |
| Duration |
Few days |
Up to many months, or years |
| Outcomes |
Resolution, abscess formation, chronic inflammation |
Tissue destruction, fibrosis |
Clinical signs
The classic signs and symptoms of acute inflammation:
| English |
Latin |
| Redness |
Rubor* |
| Swelling |
Tumor A tumor or tumour is the name for a swelling or lesion formed by an abnormal growth of cells . Tumor is not synonymous with cancer. A tumor can be benign, pre-malignant or malignant, whereas cancer is by definition malignant....
/Turgor* |
| Heat |
CalorIn physics and thermodynamics, heat is the process of energy transfer from one body or system due to thermal contact, which in turn is defined as an energy transfer to a body in any other way than due to work performed on the body....
* |
| Pain |
Dolor Physical Pain is the unpleasant feeling common to a headache and a stubbed toe. It typically consists of negative affect and aversion, and has location, duration, intensity and a distinctive quality...
* |
| Loss of function |
Functio laesa Functio laesa is a term used in medicine to refer to a loss of function or a disturbance of function.It was identified as the fifth sign of acute inflammation by Galen, who added it to the four signs identified by Celsus ....
** |
All the above signs may be observed in specific instances, but no single sign must, as a matter of course, be present.
These are the original, so called, "cardinal signs" of inflammation.*
Functio laesa is a bit of an apocryphal notion, as it is not really unique to inflammation and is a characteristic of many disease states.** |
Acute inflammation is a short-term process, usually appearing within a few minutes or hours and ceasing upon the removal of the injurious stimulus.. It is characterized by five cardinal signs:
- rubor (redness
For a person to flush is to become markedly red in the face and often other areas of the skin, from various physiological conditions. Flushing is generally distinguished, despite a close physiological relation between them, from blushing, which is milder, generally restricted to the face, cheeks or...
),
- calor (increased heat),
- tumor (swelling
In medical parlance, swelling is the enlargement of organs caused by accumulation of excess fluid in tissues, called edema.It can occur throughout the body , or a specific part or organ can be affected...
),
- dolor (pain
Physical Pain is the unpleasant feeling common to a headache and a stubbed toe. It typically consists of negative affect and aversion, and has location, duration, intensity and a distinctive quality...
), and
- functio laesa (loss of function).
The first four (classical signs) were described by
CelsusAulus Cornelius Celsus was a Roman encyclopedist, known for his extant medical work, De Medicina, which is believed to be the only surviving section of a much larger encyclopedia. The De Medicina is a primary source on diet, pharmacy, surgery and related fields, and it is one of the best sources...
(ca 30 BC–38 AD), while
loss of function was added later by
GalenAelius Galenus or Claudius Galenus , better known as Galen of Pergamum , was a prominent Greek physician and philosopher and probably the most accomplished medical researcher of the Roman period. His theories dominated and influenced Western medical science for well over a millennium...
even though the attribution is disputed and the origination of the fifth sign has also been ascribed to
Thomas SydenhamThomas Sydenham , was an English physician. He was born at Wynford Eagle in Dorset, where his father was a gentleman of property. His brother was Colonel William Sydenham. Thomas fought for the Parliament throughout the English Civil War, and, at its end, resumed his medical studies at Oxford...
and Virchow.
Redness and heat are due to increased blood flow at body core temperature to the inflamed site; swelling is caused by accumulation of fluid; pain is due to release of chemicals that stimulate nerve endings. Loss of function has multiple causes.
These five signs appear when acute inflammation occurs on the body's surface, whereas acute inflammation of internal organs may not result in the full set. Pain only happens where the appropriate sensory nerve endings exist in the inflamed area — e.g., acute inflammation of the lung (
pneumoniaPneumonia is an inflammatory illness of the lung. Frequently, it is described as lung parenchyma/alveolar inflammation and abnormal alveolar filling with fluid ....
) does not cause pain unless the inflammation involves the
parietal pleuraThe portion of the pleura external to the pulmonary pleura lines the inner surface of the chest wall, covers the diaphragm, and is reflected over the structures occupying the middle of the thorax; this portion is termed the parietal pleura....
, which does have pain-sensitive nerve endings.
Process of acute inflammation
The process of acute inflammation is initiated by cells already present in all tissues, mainly resident macrophages, dendritic cells, histiocytes, Kuppfer cells and mastocytes. At the onset of an infection, burn, or other injuries, these cells undergo activation and release inflammatory mediators responsible for the clinical signs of inflammation. Vasodilation and its resulting increased blood flow causes the redness (
rubor) and increased heat (
calor). Increased permeability of the blood vessels results in an exudation (leakage) of
plasmaBlood plasma is the yellow liquid component of blood, in which the blood cells in whole blood would normally be suspended. It makes up about 55% of the total blood volume. It is mostly water and contains dissolved proteins, glucose, clotting factors, mineral ions, hormones and carbon dioxide...
proteins and fluid into the tissue (oedema), which manifests itself as swelling (
tumor). Some of the released mediators such as
bradykininBradykinin is a peptide that causes blood vessels to enlarge , and therefore causes blood pressure to lower. A class of drugs called ACE inhibitors, which are used to lower blood pressure, increase bradykinin further lowering blood pressure...
increase the sensitivity to pain (
hyperalgesiaHyperalgesia is an increased sensitivity to pain, which may be caused by damage to nociceptors or peripheral nerves. Temporary increased sensitivity to pain also occurs as part of sickness behavior, the evolved response to infection.[Hart, B. L. "Biological basis of the behavior...]
,
dolor). The mediator molecules also alter the blood vessels to permit the migration of leukocytes, mainly neutrophils, outside of the blood vessels (extravasation) into the tissue. The neutrophils migrate along a chemotactic gradient created by the local cells to reach the site of injury. The loss of function (
functio laesa) is probably the result of a neurological reflex in response to pain.
In addition to cell-derived mediators, several acellular biochemical cascade systems consisting of preformed plasma proteins act in parallel to initiate and propagate the inflammatory response. These include the
complement systemThe complement system is a biochemical cascade that helps clear pathogens from an organism. It is part of the larger immune system that is not adaptable and does not change over the course of an individual's lifetime; as such it belongs to the innate immune system...
activated by bacteria, and the coagulation and fibrinolysis systems activated by
necrosisNecrosis is the premature death of cells and living tissue. Necrosis is caused by external factors, such as infection, toxins , or trauma. This is in contrast to apoptosis, which is a naturally occurring cause of cellular death...
, e.g. a burn or a trauma.
The acute inflammatory response requires constant stimulation to be sustained. Inflammatory mediators have short half lives and are quickly degraded in the tissue. Hence, inflammation ceases once the stimulus has been removed.
Exudative component
The
exudative component involves the movement of plasma fluid, containing important
proteinProteins are organic compounds made of amino acids arranged in a linear chain and folded into a globular form. The amino acids in a polymer chain are joined together by the peptide bonds between the carboxyl and amino groups of adjacent amino acid residues...
s such as
fibrinFibrin is a fibrous protein involved in the clotting of blood, and is non globular. It is a fibrillar protein that is polymerised to form a "mesh" that forms a hemostatic plug or clot over a wound site.Fibrin is made from fibrinogen, a soluble plasma glycoprotein that is synthesised by the liver...
and immunoglobulins (antibodies), into inflamed tissue. This movement is achieved via the chemically induced dilation and increased permeability of
blood vesselThe blood vessels are the part of the circulatory system that transport blood throughout the body. There are three major types of blood vessels: the arteries, which carry the blood away from the heart, the capillaries, which enable the actual exchange of water and chemicals between the blood and...
s, which results in a net loss of
blood plasmaBlood plasma is the yellow liquid component of blood, in which the blood cells in whole blood would normally be suspended. It makes up about 55% of the total blood volume. It is mostly water and contains dissolved proteins, glucose, clotting factors, mineral ions, hormones and carbon dioxide...
. The increased collection of fluid into the tissue causes it to swell (
edemaEdema or oedema , formerly known as dropsy or hydropsy, is an abnormal accumulation of fluid beneath the skin, or in one or more cavities of the body...
).
Vascular changes
Acute inflammation is characterised by marked vascular changes, including
vasodilationVasodilation refers to the widening of blood vessels resulting from relaxation of smooth muscle cells within the vessel walls, particularly in the large arteries, smaller arterioles and large veins. The process is essentially the opposite of vasoconstriction, or the narrowing of blood vessels. When...
, increased permeability, and the slowing of blood flow, which are induced by the actions of various inflammatory mediators. Vasodilation occurs first at the
arterioleAn arteriole is a small diameter blood vessel in the microcirculation that extends and branches out from an artery and leads to capillaries. Arterioles have thin muscular walls and are the primary site of vascular resistance...
level, progressing to the
capillaryCapillaries are the smallest of a body's blood vessels and are part of the microcirculation. They are only 1 cell thick. These microvessels, measuring 5-10 μm in diameter, connect arterioles and venules, and enable the exchange of water, oxygen, carbon dioxide, and many other nutrient and waste...
level, and brings about a net increase in the amount of blood present, causing the redness and heat of inflammation. Increased permeability of the vessels results in the movement of
plasmaBlood plasma is the yellow liquid component of blood, in which the blood cells in whole blood would normally be suspended. It makes up about 55% of the total blood volume. It is mostly water and contains dissolved proteins, glucose, clotting factors, mineral ions, hormones and carbon dioxide...
into the tissues, with resultant
stasis due to the increase in the concentration of the cells within blood - a condition characterised by enlarged vessels packed with cells. Stasis allows leukocytes to marginate (move) along the
endotheliumThe endothelium is the thin layer of cells that line the interior surface of blood vessels, forming an interface between circulating blood in the lumen and the rest of the vessel wall. Endothelial cells line the entire circulatory system, from the heart to the smallest capillary...
, a process critical to their recruitment into the tissues. Normal flowing blood prevents this, as the
shearing forceA shear stress, denoted , is defined as a stress which is applied parallel or tangential to a face of a material, as opposed to a normal stress which is applied perpendicularly.-General shear stress:...
along the periphery of the vessels moves cells in the blood into the middle of the vessel.
Plasma cascade systems
- The complement system
The complement system is a biochemical cascade that helps clear pathogens from an organism. It is part of the larger immune system that is not adaptable and does not change over the course of an individual's lifetime; as such it belongs to the innate immune system...
, when activated, results in the increased removal of pathogens via opsonisation and phagocytosisPhagocytosis is the cellular process of phagocytes and protists of engulfing solid particles by the cell membrane to form an internal phagosome...
.
- The kinin system generates proteins capable of sustaining vasodilation and other physical inflammatory effects.
- The coagulation system or clotting cascade which forms a protective protein mesh over sites of injury.
- The fibrinolysis system, which acts in opposition to the coagulation system, to counterbalance clotting and generate several other inflammatory mediators.
Plasma derived mediators
* non-exhaustive list
| Name |
Produced by |
Description |
BradykininBradykinin is a peptide that causes blood vessels to enlarge , and therefore causes blood pressure to lower. A class of drugs called ACE inhibitors, which are used to lower blood pressure, increase bradykinin further lowering blood pressure...
|
Kinin system |
A vasoactive protein which is able to induce vasodilation, increase vascular permeability, cause smooth muscle contraction, and induce pain. |
| C3 Complement component 3, often simply called C3, is a protein of the immune system. It plays a central role in the complement system and contributes to innate immunity. In humans it is encoded on chromosome 19 by a gene called C3.-Function:...
|
Complement system The complement system is a biochemical cascade that helps clear pathogens from an organism. It is part of the larger immune system that is not adaptable and does not change over the course of an individual's lifetime; as such it belongs to the innate immune system...
|
Cleaves to produce C3a and C3b. C3a stimulates histamine release by mast cells, thereby producing vasodilation. C3b is able to bind to bacterial cell walls and act as an opsonin An opsonin is any molecule that acts as a binding enhancer for the process of phagocytosis, for example, by coating the negatively-charged molecules on the membrane.-Mechanism:...
, which marks the invader as a target for phagocytosisPhagocytosis is the cellular process of phagocytes and protists of engulfing solid particles by the cell membrane to form an internal phagosome...
. |
C5aC5a is a protein fragment released from complement component C5. In humans, the polypeptide contains 74 amino acids. NMR spectroscopy proved that the molecule is composed of four helices and loops connecting the helices. On the N terminus a short 1.5 turn helix is also present. The longest helix...
|
Complement system The complement system is a biochemical cascade that helps clear pathogens from an organism. It is part of the larger immune system that is not adaptable and does not change over the course of an individual's lifetime; as such it belongs to the innate immune system...
|
Stimulates histamine release by mast cells, thereby producing vasodilation. It is also able to act as a chemoattractantChemoattractants are inorganic or organic substances possessing chemotaxis inducer effect in motile cells. Effects of chemoattractants are elicited via described or hypothetic chemotaxis receptors, the chemoattractant moiety of a ligand is target cell specific and concentration dependent. Most...
to direct cells via chemotaxis to the site of inflammation. |
Factor XIIHageman factor is a plasma protein also known as factor XII. It is the zymogen form of factor XIIa, an enzyme of the serine protease class. In humans, factor XII is encoded by the F12 gene.-Function:...
(Hageman Factor) |
LiverThe liver is a vital organ present in vertebrates and some other animals; it has a wide range of functions, including detoxification, protein synthesis, and production of biochemicals necessary for digestion...
|
A protein which circulates inactively, until activated by collagen, platelets, or exposed basement membrane The basement membrane is a thin sheet of fibers that underlies the epithelium, which lines the cavities and surfaces of organs, or the endothelium, which lines the interior surface of blood vessels.- Composition :...
s via conformational changeA macromolecule is usually flexible and dynamic. It can change its shape in response to changes in its environment or other factors; each possible shape is called a conformation, and a transition between them is called a conformational change...
. When activated, it in turn is able to activate three plasma systems involved in inflammation: the kinin system, fibrinolysis system, and coagulation system. |
| Membrane attack complex |
Complement system The complement system is a biochemical cascade that helps clear pathogens from an organism. It is part of the larger immune system that is not adaptable and does not change over the course of an individual's lifetime; as such it belongs to the innate immune system...
|
A complex of the complement proteins C5b, C6 Complement component 6 is a protein involved in the complement system....
, C7Complement component 7 is a protein involved in the complement system....
, C8Complement component 8 is a protein involved in the complement system....
, and multiple units of C9Complement component 9 is a protein involved in the complement system....
. The combination and activation of this range of complement proteins forms the membrane attack complex, which is able to insert into bacterial cell walls and causes cell lysis with ensuing death. |
| Plasmin Plasmin is an important enzyme present in blood that degrades many blood plasma proteins, most notable, fibrin clots. The degradation of fibrin is termed fibrinolysis...
|
Fibrinolysis system |
Able to break down fibrin clots, cleave complement protein C3, and activate Factor XII. |
ThrombinThrombin also commonly called pro-thrombin is a coagulation protein in the blood stream that has many effects in the coagulation cascade...
|
Coagulation system |
Cleaves the soluble plasma protein fibrinogen to produce insoluble fibrin Fibrin is a fibrous protein involved in the clotting of blood, and is non globular. It is a fibrillar protein that is polymerised to form a "mesh" that forms a hemostatic plug or clot over a wound site.Fibrin is made from fibrinogen, a soluble plasma glycoprotein that is synthesised by the liver...
, which aggregates to form a blood clot. Thrombin can also bind to cells via the PAR1Protease-activated receptors are a subfamily of related G protein-coupled receptors that are activated by cleavage of part of their extracellular domain. They are highly expressed in platelets, but also on endothelial cells, myocytes and neurons....
receptor to trigger several other inflammatory responses, such as production of chemokineChemokines are a family of small cytokines, or proteins secreted by cells. Their name is derived from their ability to induce directed chemotaxis in nearby responsive cells; they are chemotactic cytokines...
s and nitric oxideNitric oxide or nitrogen monoxide is a chemical compound with chemical formula NO. This gas is an important signaling molecule in the body of mammals, including humans, and is an extremely important intermediate in the chemical industry...
. |
Cellular component
The
cellular component involves leukocytes, which normally reside in blood and must move into the inflamed tissue via
extravasation to aid in inflammation. Some act as
phagocytePhagocytes are the white blood cells that protect the body by ingesting harmful foreign particles, bacteria, and dead or dying cells. Their name comes from the Greek phagein, "to eat" or "devour", and "-cyte", the suffix in biology denoting "cell", from the Greek kutos, "hollow vessel". They are...
s, ingesting bacteria, viruses, and cellular debris. Others release enzymatic
granuleIn cell biology, a granule can be any structure barely visible by light microscopy. The term is most often used to describe a secretory vesicle.-Leukocytes:...
s which damage pathogenic invaders. Leukocytes also release inflammatory mediators which develop and maintain the inflammatory response. Generally speaking, acute inflammation is mediated by
granulocyteGranulocytes are a category of white blood cells characterised by the presence of granules in their cytoplasm. They are also called polymorphonuclear leukocytes because of the varying shapes of the nucleus, which is usually lobed into three segments...
s, while chronic inflammation is mediated by mononuclear cells such as
monocyteMonocyte is a type of white blood cell, part of the human body's immune system. Monocytes have two main functions in the immune system: replenish resident macrophages and dendritic cells under normal states, and in response to inflammation signals, monocytes can move quickly Monocyte is a type of...
s and
lymphocyteA lymphocyte is a type of white blood cell in the vertebrate immune system.By their appearance under the light microscope, there are two broad categories of lymphocytes, namely the large granular lymphocytes and the small lymphocytes. Functionally distinct subsets of lymphocytes correlate with...
s.
Leukocyte extravasation
Various leukocytes are critically involved in the initiation and maintenance of inflammation. These cells must be able to get to the site of injury from their usual location in the blood, therefore mechanisms exist to recruit and direct leukocytes to the appropriate place. The process of leukocyte movement from the blood to the tissues through the blood vessels is known as
extravasation, and can be divided up into a number of broad steps:
- Leukocyte localisation and recruitment to the endothelium local to the site of inflammation – involving margination and adhesion to the endothelial cells: Recruitment of leukocytes is receptor-mediated. The products of inflammation, such as histamine
Histamine is a biogenic amine involved in local immune responses as well as regulating physiological function in the gut and acting as a neurotransmitter. Histamine triggers the inflammatory response. As part of an immune response to foreign pathogens, histamine is produced by basophils and by...
, promote the immediate expression of P-selectinP-selectin is a cell adhesion molecule on the surfaces of activated endothelial cells, which line the inner surface of blood vessels, and activated platelets...
on endothelial cell surfaces. This receptor binds weakly to carbohydrate ligands on leukocyte surfaces and causes them to "roll" along the endothelial surface as bonds are made and broken. Cytokines from injured cells induce the expression of E-selectinE-selectin, also known as CD62E, is a cell adhesion molecule expressed only on endothelial cells activated by cytokines. Like other selectins, it plays an important part in inflammation. In humans, E-selectin is encoded by the SELE gene.- Ligands :...
on endothelial cells, which functions similarly to P-selectin. Cytokines also induce the expression of integrinIntegrins are receptors that mediate attachment between a cell and the tissues surrounding it, which may be other cells or the extracellular matrix . They also play a role in cell signaling and thereby define cellular shape, mobility, and regulate the cell cycle.Typically, receptors inform a cell...
ligands on endothelial cells, which further slow leukocytes down. These weakly bound leukocytes are free to detach if not activated by chemokines produced in injured tissue. Activation increases the affinity of bound integrin receptors for ligands on the endothelial cell surface, firmly binding the leukocytes to the endothelium.
- Migration across the endothelium, known as transmigration, via the process of diapedesis: Chemokine gradients stimulate the adhered leukocytes to move between endothelial cells and pass the basement membrane into the tissues.
- Movement of leukocytes within the tissue via chemotaxis
Chemotaxis is the phenomenon in which bodily cells, bacteria, and other single-cell or multicellular organisms direct their movements according to certain chemicals in their environment. This is important for bacteria to find food by swimming towards the highest concentration of food molecules, or...
: Leukocytes reaching the tissue interstitium bind to extracellular matrixIn biology, the extracellular matrix is the extracellular part of animal tissue that usually provides structural support to the animal cells in addition to performing various other important functions. The extracellular matrix is the defining feature of connective tissue in animals.Extracellular...
proteins via expressed integrins and CD44The CD44 protein is a cell-surface glycoprotein involved in cell-cell interactions, cell adhesion and migration. It is a receptor for hyaluronic acid and can also interact with other ligands, such as osteopontin, collagens, and matrix metalloproteinases...
to prevent their loss from the site. ChemoattractantChemoattractants are inorganic or organic substances possessing chemotaxis inducer effect in motile cells. Effects of chemoattractants are elicited via described or hypothetic chemotaxis receptors, the chemoattractant moiety of a ligand is target cell specific and concentration dependent. Most...
s cause the leukocytes to move along a chemotactic gradient towards the source of inflammation.
Cell derived mediators
* non-exhaustive list
| Name |
Type |
Source |
Description |
| Lysosome granules In cell biology, a granule can be any structure barely visible by light microscopy. The term is most often used to describe a secretory vesicle.-Leukocytes:...
|
EnzymeEnzymes are proteins that catalyze chemical reactions. In enzymatic reactions, the molecules at the beginning of the process are called substrates, and the enzyme converts them into different molecules, called the products. Almost all processes in a biological cell need enzymes to occur at...
s |
Granulocyte Granulocytes are a category of white blood cells characterised by the presence of granules in their cytoplasm. They are also called polymorphonuclear leukocytes because of the varying shapes of the nucleus, which is usually lobed into three segments...
s |
These cells contain a large variety of enzymes which perform a number of functions. Granules can be classified as either specific Specific granules are secretory vesicles found exclusively in cells of the immune system called granulocytes. They are also known as secondary granules....
or azurophilAzurophil is the term used to refer to objects that are readily staining with an azure dye. The term is used especially in reference to certain cytoplasmic granules in white blood cells, particularly hyperchromatin and reddish purple granules of certain blood cells.As another example, neutrophils...
ic depending upon the contents, and are able to break down a number of substances, some of which may be plasma-derived proteins which allow these enzymes to act as inflammatory mediators. |
HistamineHistamine is a biogenic amine involved in local immune responses as well as regulating physiological function in the gut and acting as a neurotransmitter. Histamine triggers the inflammatory response. As part of an immune response to foreign pathogens, histamine is produced by basophils and by...
|
Vasoactive amineAmines are organic compounds and functional groups that contain a basic nitrogen atom with a lone pair. Amines are derivatives of ammonia, wherein one or more hydrogen atoms have been replaced by a substituent such as an alkyl or aryl group. Important amines include amino acids, biogenic amines,...
|
Mast cells, basophils, platelets |
Stored in preformed granules, histamine is released in response to a number of stimuli. It causes arteriole An arteriole is a small diameter blood vessel in the microcirculation that extends and branches out from an artery and leads to capillaries. Arterioles have thin muscular walls and are the primary site of vascular resistance...
dilation and increased venous permeability. |
| IFN-γ |
Cytokine Cytokines are any of a number of substances that are secreted by specific cells of the immune system which carry signals locally between cells, and thus have an effect on other cells. They are a category of signaling molecules that are used extensively in cellular communication. They are proteins,...
|
T-cells, NK cells |
Antiviral, immunoregulatory, and anti-tumour properties. This interferon was originally called macrophage-activating factor, and is especially important in the maintenance of chronic inflammation. |
| IL-8 Interleukin-8 is a chemokine produced by macrophages and other cell types such as epithelial cells. It is also synthesized by endothelial cells, which store IL-8 in their storage vesicles, the Weibel-Palade bodies. In humans, the interleukin-8 protein is encoded by the IL8 gene.There are more...
|
Chemokine Chemokines are a family of small cytokines, or proteins secreted by cells. Their name is derived from their ability to induce directed chemotaxis in nearby responsive cells; they are chemotactic cytokines...
|
Primarily macrophage Macrophages are white blood cells within tissues, produced by the division of monocytes. Human macrophages are about in diameter...
s |
Activation and chemoattraction of neutrophils, with a weak effect on monocytes and eosinophils. |
Leukotriene B4Leukotriene B4 is a leukotriene involved in inflammation. It is produced from leukocytes in response to inflammatory mediators and is able to induce the adhesion and activation of leukocytes on the endothelium, allowing them to bind to and cross it into the tissue...
|
Eicosanoid In biochemistry, eicosanoids are signaling molecules made by oxygenation of twenty-carbon essential fatty acids, .They exert complex control over many bodily systems, mainly in inflammation or immunity, and as messengers in the central nervous system....
|
Leukocytes |
Able to mediate leukocyte adhesion and activation, allowing them to bind to the endothelium and migrate across it. In neutrophils, it is also a potent chemoattractant, and is able to induce the formation of reactive oxygen species and the release of lysosome enzymes by these cells. |
Nitric oxideNitric oxide or nitrogen monoxide is a chemical compound with chemical formula NO. This gas is an important signaling molecule in the body of mammals, including humans, and is an extremely important intermediate in the chemical industry...
|
Soluble gas |
Macrophages, endothelial cells, some neurons |
Potent vasodilator, relaxes smooth muscle, reduces platelet aggregation, aids in leukocyte recruitment, direct antimicrobial activity in high concentrations. |
| Prostaglandin A prostaglandin is any member of a group of lipid compounds that are derived enzymatically from fatty acids and have important functions in the animal body. Every prostaglandin contains 20 carbon atoms, including a 5-carbon ring....
s |
Eicosanoid In biochemistry, eicosanoids are signaling molecules made by oxygenation of twenty-carbon essential fatty acids, .They exert complex control over many bodily systems, mainly in inflammation or immunity, and as messengers in the central nervous system....
|
Mast cells |
A group of lipids which can cause vasodilation, fever, and pain. |
TNF-α and IL-1Interleukin-1 is one of the first cytokines ever described. Its initial discovery was as a factor that could induce fever, control lymphocytes, increase the number of bone marrow cells and cause degeneration of bone joints...
|
Cytokine Cytokines are any of a number of substances that are secreted by specific cells of the immune system which carry signals locally between cells, and thus have an effect on other cells. They are a category of signaling molecules that are used extensively in cellular communication. They are proteins,...
s |
Primarily macrophages |
Both affect a wide variety of cells to induce many similar inflammatory reactions: fever, production of cytokines, endothelial gene regulation, chemotaxis, leukocyte adherence, activation of fibroblast A fibroblast is a type of cell that synthesizes the extracellular matrix and collagen, the structural framework for animal tissues, and plays a critical role in wound healing...
s. Responsible for the systemic effects of inflammation, such as loss of appetite and increased heart rate. |
Morphologic patterns
Specific patterns of acute and chronic inflammation are seen during particular situations that arise in the body, such as when inflammation occurs on an epithelial surface, or
pyogenicPyogenic refers to bacterial infections that make pus.The pus is mostly composed of dead neutrophils that are destroyed by bacteria such as Streptococcus pyogenes and Staphylococcus aureus through the release of leukocidins...
bacteria are involved.
- Granulomatous inflammation: Characterised by the formation of granuloma
Granuloma is a medical term for a ball-like collection of immune cells which forms when the immune system attempts to wall off substances that it perceives as foreign but is unable to eliminate. Such substances include infectious organisms such as bacteria and fungi as well as other materials such...
s, they are the result of a limited but diverse number of diseases, which include among others tuberculosisTuberculosis is a common and often deadly infectious disease caused by mycobacteria...
, leprosyLeprosy , or Hansen's disease , is a chronic disease caused by the bacteria Mycobacterium leprae and Mycobacterium lepromatosis. Leprosy is primarily a granulomatous disease of the peripheral nerves and mucosa of the upper respiratory tract; skin lesions are the primary external symptom...
, and syphilisSyphilis is a sexually transmitted disease caused by the spirochetal bacterium Treponema pallidum subspecies pallidum. The route of transmission of syphilis is almost always through sexual contact, although there are examples of congenital syphilis via transmission from mother to child in utero.The...
.
- Fibrinous inflammation: Inflammation resulting in a large increase in vascular permeability allows fibrin
Fibrin is a fibrous protein involved in the clotting of blood, and is non globular. It is a fibrillar protein that is polymerised to form a "mesh" that forms a hemostatic plug or clot over a wound site.Fibrin is made from fibrinogen, a soluble plasma glycoprotein that is synthesised by the liver...
to pass through the blood vessels. If an appropriate procoagulative stimulus is present, such as cancer cells, a fibrinous exudate is deposited. This is commonly seen in serous cavitiesIn anatomy, a serous membrane is a smooth membrane consisting of a thin layer of cells which excrete serous fluid. Serous membranes line and enclose several body cavities, known as serous cavities, where they secrete a lubricating fluid which reduces friction from muscle movement...
, where the conversion of fibrinous exudate into a scar can occur between serous membranes, limiting their function.
- Purulent inflammation: Inflammation resulting in large amount of pus
Pus is a whitish-yellow, yellow or yellow-brown exudate produced by vertebrates during inflammatory pyogenic bacterial infections. An accumulation of pus in an enclosed tissue space is known as an abscess, while a visible collection of pus within or beneath the epidermis is known as a pustule or...
, which consists of neutrophils, dead cells, and fluid. Infection by pyogenic bacteria such as staphylococci is characteristic of this kind of inflammation. Large, localised collections of pus enclosed by surrounding tissues are called abscessAn abscess is a collection of pus that has accumulated in a cavity formed by the tissue on the basis of an infectious process or other foreign materials...
es.
- Serous inflammation: Characterised by the copious effusion of non-viscous serous fluid, commonly produced by mesothelial cells of serous membrane
In anatomy, a serous membrane is a smooth membrane consisting of a thin layer of cells which excrete serous fluid. Serous membranes line and enclose several body cavities, known as serous cavities, where they secrete a lubricating fluid which reduces friction from muscle movement...
s, but may be derived from blood plasma. Skin blisterA blister is a small pocket of fluid within the upper layers of the skin, typically caused by forceful rubbing , burning, freezing, chemical exposure or infection. Most blisters are filled with a clear fluid called serum or plasma...
s exemplify this pattern of inflammation.
- Ulcerative inflammation: Inflammation occurring near an epithelium can result in the necrotic loss of tissue from the surface, exposing lower layers. The subsequent excavation in the epithelium is known as an ulcer.
Inflammatory disorders
Abnormalities associated with inflammation comprise a large, officially unrelated group of disorders which underlie a vast variety of human diseases. The immune system is often involved with inflammatory disorders, demonstrated in both allergic reactions and some myopathies, with many immune system disorders resulting in abnormal inflammation. Non-immune diseases with a etiological origins in inflammatory processes are thought to include cancer,
atherosclerosisAtherosclerosis is the condition in which an artery wall thickens as the result of a build-up of fatty materials such as cholesterol...
, and
ischaemic heart diseaseIschaemic or ischemic heart disease , or myocardial ischaemia, is a disease characterized by reduced blood supply to the heart muscle, usually due to coronary artery disease...
.
A large variety of proteins are involved in inflammation, and any one of them is open to a genetic mutation which impairs or otherwise dysregulates the normal function and expression of that protein.
Examples of disorders associated with inflammation include:
Allergies
An allergic reaction, formally known as type 1 hypersensitivity, is the result of an inappropriate immune response triggering inflammation. A common example is
hay feverHay Fever is a comic play written by Noël Coward in 1924 and first produced in 1925 with Marie Tempest as the first Judith Bliss.Laura Hope Crewes played the role in New York...
, which is caused by a hypersensitive response by skin
mast cellA mast cell is a resident cell of several types of tissues and contains many granules rich in histamine and heparin. Although best known for their role in allergy and anaphylaxis, mast cells play an important protective role as well, being intimately involved in wound healing and defense against...
s to
allergenAn allergen is a nonparasitic antigen capable of stimulating a type-I hypersensitivity reaction in atopic individuals.Most humans mount significant Immunoglobulin E responses only as a defense against parasitic infections. However, some individuals mount an IgE response against common...
s. Pre-sensitised mast cells respond by
degranulatingDegranulation is a cellular process that releases antimicrobial cytotoxic molecules from secretory vesicles called granules found inside some cells...
, releasing
vasoactiveA hormone, drug or chemical which is capable of eliciting vasoconstrictive or vasodilative action on the vasculature. Examples include histamine and heparin, released at the sites of infection which stimulate vasodilation of arterioles and facilaitate an inflammatory response at the site of...
chemicals such as histamine. These chemicals propagate an excessive inflammatory response characterised by blood vessel dilation, production of pro-inflammatory molecules, cytokine release, and recruitment of leukocytes. Severe inflammatory response may mature into a systemic response known as
anaphylaxisAnaphylaxis is an acute systemic and severe type I hypersensitivity allergic reaction in humans and other mammals. The term comes from the Greek words ανα ana and φύλαξις phylaxis . Minute amounts of allergens may cause a life-threatening anaphylactic reaction...
.
Other
hypersensitivityHypersensitivity refers to undesirable reactions produced by the normal immune system. Hypersensitivity reactions require a pre-sensitized state of the host. The four-group classification was expounded by P. H. G...
reactions (
type 2 and
type 3) are mediated by antibody reactions and induce inflammation by attracting leukocytes which damage surrounding tissue.
Myopathies
Inflammatory myopathies are caused by the immune system inappropriately attacking components of muscle, leading to signs of muscle inflammation. They may occur in conjunction with other immune disorders, such as systemic sclerosis, and include
dermatomyositisDermatomyositis is a connective-tissue disease related to polymyositis that is characterized by inflammation of the muscles and the skin.-Causes:The cause is unknown, but it may result from either a viral infection or an autoimmune reaction...
,
polymyositisPolymyositis is a type of chronic inflammatory myopathy related to dermatomyositis and inclusion body myositis. Polymyositis means 'many muscle inflammation'.-Presentation:...
, and
inclusion body myositisInclusion body myositis is an inflammatory muscle disease, characterized by slowly progressive weakness and wasting of both distal and proximal muscles, most apparent in the muscles of the arms and legs...
.
Leukocyte defects
Due to the central role of leukocytes in the development and propagation of inflammation, defects in leukocyte function often result in a decreased capacity for inflammatory defense with subsequent vulnerability to infection. Dysfunctional leukocytes may be unable to correctly bind to blood vessels due to surface receptor mutations, digest bacteria (
Chediak-Higashi syndromeChediak–Higashi syndrome is a rare autosomal recessive disorder that affects multiple systems of the body, and arises from a mutation in the lysosomal trafficking regulator gene, LYST. It occurs in humans, cattle, white tigers, blue Persian cats and the only known captive albino...
), or produce
microbicideIn the HIV and STD prevention field the word microbicides refers to a new type of product being developed that could be used vaginally or rectally to reduce a person's risk of HIV infection and possibly other sexually transmitted infections...
s (
chronic granulomatous diseaseChronic granulomatous disease is a diverse group of hereditary diseases in which certain cells of the immune system have difficulty forming the reactive oxygen compounds used to kill certain ingested pathogens...
). Additionally, diseases affecting the
bone marrowBone marrow is the flexible tissue found in the hollow interior of bones. In adults, marrow in large bones produces new blood cells. It constitutes 4% of total body weight, i.e...
may result in abnormal or few leukocytes.
Pharmacological
Certain drugs or exogenic chemical compounds are known to affect inflammation.
Vitamin AVitamin A is linked to a family of similarly shaped molecules, the retinoids, which complete the remainder of the vitamin sequence. Its important part is the retinyl group, which can be found in several forms. In foods of animal origin, the major form of vitamin A is an ester, primarily retinyl...
deficiency causes an increase in inflammatory responses, and
anti-inflammatoryAnti-inflammatory refers to the property of a substance or treatment that reduces inflammation. Anti-inflammatory drugs make up about half of analgesics, remedying pain by reducing inflammation as opposed to opioids which affect the brain.-Medications:...
drugs work specifically by inhibiting normal inflammatory components.
Cancer
Inflammation orchestrates the microenvironment around tumours, contributing to proliferation, survival and migration. Cancer cells use selectins, chemokines and their receptors for invasion, migration and metastasis. On the other hand, many cells of the immune system contribute to
cancer immunologyCancer immunology is the study of interactions between the immune system and cancer cells . It is also a growing field of research that aims to discover innovative cancer immunotherapies to treat and retard progression of this disease...
, suppressing cancer.
Termination
The inflammatory response must be actively terminated when no longer needed to prevent unnecessary "bystander" damage to tissues. Failure to do so results in chronic inflammation, cellular destruction, and attempts to heal the inflamed tissue. One intrinsic mechanism employed to terminate inflammation is the short half-life of inflammatory mediators
in vivo. They have a limited time frame to affect their target before breaking down into non-functional components, therefore constant inflammatory stimulation is needed to propagate their effects.
Active mechanisms which serve to terminate inflammation include:
- TGF-β from macrophages
- Anti-inflammatory lipoxin
Lipoxins are a series of anti-inflammatory mediators. Lipoxins are short lived endogenously produced nonclassic eicosanoids whose appearance in inflammation signals the resolution of inflammation....
s
- Inhibition of pro-inflammatory molecules, such as leukotrienes
Systemic effects
An infectious organism can escape the confines of the immediate tissue via the
circulatory system- [Headline text]--75.137.171.242 01:21, 21 October 2009 :bThe circulatory system is an organ system that passes nutrients , gases, hormones, blood cells, nitrogen waste products, etc. to and from cells in the body to help fight diseases and help stabilize body temperature and pHb to maintain...
or
lymphatic systemThe lymphatic system in vertebrates is a network of conduits that carry a clear fluid called lymph. It also includes the lymphoid tissue through which the lymph travels. Lymphoid tissue is found in many organs, particularly the lymph nodes, and in the lymphoid follicles associated with the...
, where it may spread to other parts of the body. If an organism is not contained by the actions of acute inflammation it may gain access to the lymphatic system via nearby
lymph vesselIn anatomy, lymph vessels are thin walled, valved structures that carry lymph. As part of the lymphatic system, lymph vessels are complementary to the vascular system. Lymph vessels are lined by endothelial cells, and deep to that have a thin layer of smooth muscles, and adventitia that bind the...
s. An infection of the lymph vessels is known as
lymphangitisLymphangitis is an inflammation of the lymphatic channels that occurs as a result of infection at a site distal to the channel. The most common cause of Lymphangitis in humans is Streptococcus Pyogenes...
, and infection of a lymph node is known as lymphadenitis. A pathogen can gain access to the bloodstream through lymphatic drainage into the circulatory system.
When inflammation overwhelms the host,
systemic inflammatory response syndromeIn medicine, systemic inflammatory response syndrome is an inflammatory state affecting the whole body, frequently in response to infection, but not necessarily so...
is diagnosed. When it is due to
infectionAn infection is the detrimental colonization of a host organism by a foreign species. In an infection, the infecting organism seeks to utilize the host's resources to multiply, usually at the expense of the host. The infecting organism, or pathogen, interferes with the normal functioning of the...
, the term
sepsisSepsis is a serious medical condition that is characterized by a whole-body inflammatory state and the presence of a known or suspected infection.
is applied, with bacteremiaBacteremia is the presence of bacteria in the blood. The blood is normally a sterile environment, so the detection of bacteria in the blood is always abnormal....
being applied specifically for bacterial sepsis and viremiaViremia is a medical condition where viruses enter the bloodstream and hence have access to the rest of the body. It is similar to bacteremia, a condition where bacteria enter the bloodstream.- Primary versus Secondary :...
specifically to viral sepsis. VasodilationVasodilation refers to the widening of blood vessels resulting from relaxation of smooth muscle cells within the vessel walls, particularly in the large arteries, smaller arterioles and large veins. The process is essentially the opposite of vasoconstriction, or the narrowing of blood vessels. When...
and organ dysfunction are serious problems associated with widespread infection that may lead to septic shockSeptic shock is a serious medical condition caused by decreased tissue perfusion and oxygen delivery as a result of infection and sepsis, though the microbe may be systemic or localized to a particular site. It can cause multiple organ dysfunction syndrome and death...
and death.
Acute-phase proteins
Inflammation also induces high systemic levels of acute-phase proteins. In acute inflammation, these proteins prove beneficial, however in chronic inflammation they can contribute to amyloidosisIn medicine, amyloidosis refers to a variety of conditions in which amyloid proteins are abnormally deposited in organs and/or tissues. A protein is described as being amyloid if, due to an alteration in its secondary structure, it takes on a particular aggregated insoluble form similar to the...
. These proteins include C-reactive proteinC-reactive protein is a protein found in the blood, the levels of which rise in response to inflammation ....
, serum amyloid ASerum amyloid A proteins are a family of apolipoproteins associated with high-density lipoprotein in plasma. Different isoforms of SAA are expressed constitutively at different levels or in response to inflammatory stimuli . These proteins are produced predominantly by the liver...
, and serum amyloid P, vasopressinArginine vasopressin , also known as vasopressin, argipressin or antidiuretic hormone , is a hormone found in most mammals, including humans. Vasopressin is a peptide hormone. It is derived from a preprohormone precursor that is synthesized in the hypothalamus and stored in vesicles at the...
, which cause a range of systemic effects including:
Leukocyte numbers
Inflammation often affects the numbers of leukocytes present in the body:
- Leukocytosis
Leukocytosis is a raised white blood cell count above the normal range. This increase in leukocytes is usually accompanied by a "left shift" in the ratio of immature to mature neutrophils...
is often seen during inflammation induced by infection, where it results in a large increase in the amount of leukocytes in the blood, especially immature cells. Leukocyte numbers usually increase to between 15 000 and 20 000 cells per mlThe litre or liter is a unit of volume. There are two official symbols: the Latin letter L in lower and upper case . The lower case L is also often written as a cursive ℓ, though this symbol has no official approval by any international bureau...
, but extreme cases can see it approach 100 000 cells per ml. Bacterial infection usually results in an increase of neutrophils, creating neutrophiliaNeutrophilia is a condition where a person has a high number of neutrophil granulocytes in their blood.-Causes:...
, whereas diseases such as asthmaAsthma is a predisposition to chronic inflammation of the lungs in which the airways are reversibly narrowed. Asthma affects 7% of the population of the United States, and 300 million worldwide...
, hay feverHay Fever is a comic play written by Noël Coward in 1924 and first produced in 1925 with Marie Tempest as the first Judith Bliss.Laura Hope Crewes played the role in New York...
, and parasite infestation result in an increase in eosinophils, creating eosinophiliaEosinophilia is the state of having a high concentration of eosinophils in the blood. The normal concentration is between 0 and 0.5 x 109 eosinophils per litre of blood...
.
- Leukopenia
Leukopenia is a decrease in the number of white blood cells found in the blood, which places individuals at increased risk of infection....
can be induced by certain infections and diseases, including viral infection, RickettsiaRickettsia is a genus of motile, Gram-negative, non-sporeforming, highly pleomorphic bacteria that can present as cocci , rods or thread-like . Obligate intracellular parasites, the Rickettsia survival depends on entry, growth, and replication within the cytoplasm of eukaryotic host cells...
infection, some protozoaProtozoa or Cornelius protozoans Protozoa or Cornelius protozoans Protozoa or Cornelius protozoans (from Greek πρῶτον proton "first" and ζῷα zoa "animals"; singular protozoon; (the word "protozoan" is originally an adjective, used as a noun) are microorganisms classified as unicellular eukaryotes....
, tuberculosisTuberculosis is a common and often deadly infectious disease caused by mycobacteria...
, and some cancerCancer is a class of diseases in which a group of cells display uncontrolled growth , invasion , and sometimes metastasis...
s.
Systemic inflammation and obesity
With the discovery of interleukinInterleukins are a group of cytokines that were first seen to be expressed by white blood cells , The term interleukine, as a means of communication, deriving from the fact that many of these proteins are produced by leukocytes and act on leukocytes...
s (IL), the concept of systemic inflammation developed. Although the processes involved are identical to tissue inflammation, systemic inflammation is not confined to a particular tissue but involves the endotheliumThe endothelium is the thin layer of cells that line the interior surface of blood vessels, forming an interface between circulating blood in the lumen and the rest of the vessel wall. Endothelial cells line the entire circulatory system, from the heart to the smallest capillary...
and other organ systems.
High levels of several inflammation-related markers such as IL-6, IL-8Interleukin-8 is a chemokine produced by macrophages and other cell types such as epithelial cells. It is also synthesized by endothelial cells, which store IL-8 in their storage vesicles, the Weibel-Palade bodies. In humans, the interleukin-8 protein is encoded by the IL8 gene.There are more...
, and TNF-α are associated with obesityObesity is a medical condition in which excess body fat has accumulated to the extent that it may have an adverse effect on health, leading to reduced life expectancy and/or increased health problems...
. During clinical studies, inflammatory-related molecule levels were reduced and increased levels of anti-inflammatory molecules were seen within four weeks after patients began a very low calorie diet. The association of systemic inflammation with insulin resistanceInsulin resistance is the condition in which normal amounts of insulin are inadequate to produce a normal insulin response from fat, muscle and liver cells. Insulin resistance in fat cells reduces the effects of insulin and results in elevated hydrolysis of stored triglycerides in the absence of...
and atherosclerosisAtherosclerosis is the condition in which an artery wall thickens as the result of a build-up of fatty materials such as cholesterol...
is the subject of intense
research.
Outcomes
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The outcome in a particular circumstance will be determined by the tissue in which the injury has occurred and the injurious agent that is causing it. Here are the possible outcomes to inflammation:
- Resolution
The complete restoration of the inflamed tissue back to a normal status. Inflammatory measures such as vasodilation, chemical production, and leukocyte infiltration cease, and damaged parenchymaParenchyma is a term used to describe a bulk of a substance. It is used in different ways in animals and in plants.The term is New Latin, from Greek parenkhuma, visceral flesh, from parenkhein, to pour in beside : para-, beside + en-, in + khein, to pour.- In animals :The parenchyma are the...
l cells regenerate. In situations where limited or short lived inflammation has occurred this is usually the outcome.
- Fibrosis
Large amounts of tissue destruction, or damage in tissues unable to regenerate, can not be regenerated completely by the body. Fibrous scarring occurs in these areas of damage, forming a scar composed primarily of collagenCollagen is the main protein of connective tissue in animals and the most abundant protein in mammals, making up about 25% to 35% of the whole-body protein content. It is naturally found exclusively in metazoa, including sponges. In muscle tissue it serves as a major component of endomysium...
. The scar will not contain any specialized structures, such as parenchymaParenchyma is a term used to describe a bulk of a substance. It is used in different ways in animals and in plants.The term is New Latin, from Greek parenkhuma, visceral flesh, from parenkhein, to pour in beside : para-, beside + en-, in + khein, to pour.- In animals :The parenchyma are the...
l cells, hence functional impairment may occur.
- Abscess Formation
A cavity is formed containing pus, an opaque liquid containing dead white blood cells and bacteria with general debris from destroyed cells.
- Chronic inflammation
In acute inflammation, if the injurious agent persists then chronic inflammation will ensue. This process, marked by inflammation lasting many days, months or even years, may lead to the formation of a chronic woundA chronic wound is a wound that does not heal in an orderly set of stages and in a predictable amount of time the way most wounds do; wounds that do not heal within three months are often considered chronic....
. Chronic inflammation is characterised by the dominating presence of macrophages in the injured tissue. These cells are powerful defensive agents of the body, but the toxinA toxin is a poisonous substance produced by living cells or organisms ....
s they release (including reactive oxygen speciesReactive oxygen species are free radicals that contain the oxygen atom. They are very small molecules that include oxygen ions and peroxides and can be either inorganic or organic. They are highly reactive due to the presence of unpaired valence shell electrons.ROS form as a natural byproduct of...
) are injurious to the organism's own tissues as well as invading agents. Consequently, chronic inflammation is almost always accompanied by tissue destruction.
Examples
Inflammation is usually indicated by adding the suffix "-itis", as shown below. However, some conditions such as asthmaAsthma is a predisposition to chronic inflammation of the lungs in which the airways are reversibly narrowed. Asthma affects 7% of the population of the United States, and 300 million worldwide...
and pneumoniaPneumonia is an inflammatory illness of the lung. Frequently, it is described as lung parenchyma/alveolar inflammation and abnormal alveolar filling with fluid ....
do not follow this convention. More examples are available at list of types of inflammation.
See also
- Anaphylatoxin
Anaphylatoxins, or anaphylotoxins, are fragments that are produced as part of the activation of the complement system.-Functions:...
- Anti-inflammatories
Anti-inflammatory refers to the property of a substance or treatment that reduces inflammation. Anti-inflammatory drugs make up about half of analgesics, remedying pain by reducing inflammation as opposed to opioids which affect the brain.-Medications:...
- Healing
Healing is the act or process of curing or of restoring to health. Assessed physically, healing is the process by which the cells in the body regenerate and repair to reduce the size of a damaged or necrotic area....
- Interleukin
Interleukins are a group of cytokines that were first seen to be expressed by white blood cells , The term interleukine, as a means of communication, deriving from the fact that many of these proteins are produced by leukocytes and act on leukocytes...
- Lipoxin
Lipoxins are a series of anti-inflammatory mediators. Lipoxins are short lived endogenously produced nonclassic eicosanoids whose appearance in inflammation signals the resolution of inflammation....
- Substance P
In the field of neuroscience, substance P is a neuropeptide: an undecapeptide that functions as a neurotransmitter and as a neuromodulator. It belongs to the tachykinin neuropeptide family. Substance P and its closely related neuropeptide neurokinin A are produced from a polyprotein precursor...
Further reading
Kyriakis JM, Avruch J. Sounding the alarm: protein kinase cascades activated by stress and inflammation. J Biol Chem. 1996 Oct 4;271(40):24313-6. Review. PMID: 8798679
Salminen A, Kauppinen A, Suuronen T, Kaarniranta K. SIRT1 longevity factor suppresses NF-kappaB -driven immune responses: regulation of aging via NF-kappaB acetylation? Bioessays. 2008 Oct;30(10):939-42.
Rangan G, Wang Y, Harris D. NF-kappaB signalling in chronic kidney disease. Front Biosci. 2009 Jan 1;14:3496-522. Review. PMID: 19273289
External links