Interleukin-1 (IL-1) is one of the first
cytokineCytokines 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 ever described. Its initial discovery was as a factor that could induce
feverFever is a frequent medical sign that describes an increase in internal body temperature to levels above normal...
, control lymphocytes, increase the number of
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...
cells and cause degeneration of bone joints. At this time, IL-1 was known under several other names including endogenous pyrogen, lymphocyte activating factor, haemopoetin-1 and mononuclear cell factor, amongst others. It was around 1984-1985 when scientists confirmed that IL-1 was actually composed of two distinct proteins, now called
IL-1αInterleukin-1 alpha is a protein that in humans is encoded by the IL1A gene.The protein encoded by this gene is a member of the interleukin 1 cytokine family. This cytokine is a pleiotropic cytokine involved in various immune responses, inflammatory processes, and hematopoiesis...
and
IL-1βInterleukin 1, beta, also known as IL1B, is a cytokine protein which in humans is encoded by the IL1B gene. IL-1β precursor is cleaved by caspase 1 . Cytosolic thiol protease cleaves the product to form mature IL-1β....
.
The original members of the IL-1 superfamily are IL-1α, IL-1β, and the IL-1 Receptor antagonist (IL-1RA).
- IL-1α and -β are pro-inflammatory 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 involved in immune defense against infection.
- The IL-1RA is a molecule that competes for receptor binding with IL-1α and IL-1β, blocking their role in immune activation.
Recent years have seen the addition of other molecules to the IL-1 superfamily including
IL-18IL-18 or IL 18 can refer to:* Interleukin 18* Ilyushin Il-18* Illinois' 18th congressional district* Illinois Route 18...
and six more genes with structural homology to IL-1α, IL-1β or IL-1RA.
Interleukin-1 (IL-1) is one of the first
cytokineCytokines 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 ever described. Its initial discovery was as a factor that could induce
feverFever is a frequent medical sign that describes an increase in internal body temperature to levels above normal...
, control lymphocytes, increase the number of
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...
cells and cause degeneration of bone joints. At this time, IL-1 was known under several other names including endogenous pyrogen, lymphocyte activating factor, haemopoetin-1 and mononuclear cell factor, amongst others. It was around 1984-1985 when scientists confirmed that IL-1 was actually composed of two distinct proteins, now called
IL-1αInterleukin-1 alpha is a protein that in humans is encoded by the IL1A gene.The protein encoded by this gene is a member of the interleukin 1 cytokine family. This cytokine is a pleiotropic cytokine involved in various immune responses, inflammatory processes, and hematopoiesis...
and
IL-1βInterleukin 1, beta, also known as IL1B, is a cytokine protein which in humans is encoded by the IL1B gene. IL-1β precursor is cleaved by caspase 1 . Cytosolic thiol protease cleaves the product to form mature IL-1β....
.
The Interleukin-1 superfamily
The original members of the IL-1 superfamily are IL-1α, IL-1β, and the IL-1 Receptor antagonist (IL-1RA).
- IL-1α and -β are pro-inflammatory 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 involved in immune defense against infection.
- The IL-1RA is a molecule that competes for receptor binding with IL-1α and IL-1β, blocking their role in immune activation.
Recent years have seen the addition of other molecules to the IL-1 superfamily including
IL-18IL-18 or IL 18 can refer to:* Interleukin 18* Ilyushin Il-18* Illinois' 18th congressional district* Illinois Route 18...
and six more genes with structural homology to IL-1α, IL-1β or IL-1RA. These latter six members are named , , , , , and . In accord, IL-1α, IL-1β, and IL-1RA have been renamed IL-1F1, IL-1F2, and IL-1F3, respectively.
A further putative member of the IL-1 family has been recently described that is called
IL-33Interleukin 33 is a cytokine belonging to the IL-1 superfamily. IL-33 induces helper T cells, mast cells, eosinophils and basophils to produce type 2 cytokines. This cytokine was previously named NF-HEV 'nuclear factor in high endothelial venules' since it was originally identified in these...
or IL-1F11, although this name is not officially accepted in the HGNC gene family nomenclature database.
IL-1α and IL-1β
Both IL-1α and IL-1β are produced by
macrophageMacrophages are white blood cells within tissues, produced by the division of monocytes. Human macrophages are about in diameter...
s,
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
dendritic cellDendritic cells are immune cells that form part of the mammalian immune system. Their main function is to process antigen material and present it on the surface to other cells of the immune system, thus functioning as antigen-presenting cells....
s. They form an important part of the
inflammatory responseInflammation is the complex biological response of vascular tissues to harmful stimuli, such as pathogens, 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...
of the body against
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...
. These cytokines increase the expression of adhesion factors on endothelial cells to enable transmigration of leukocytes, the cells that fight pathogens, to sites of infection and re-set the
hypothalamusThe hypothalamus is a portion of the brain that contains a number of small nuclei with a variety of functions. One of the most important functions of the hypothalamus is to link the nervous system to the endocrine system via the pituitary gland ....
thermoregulatory center, leading to an increased body temperature which expresses itself as
feverFever is a frequent medical sign that describes an increase in internal body temperature to levels above normal...
. IL-1 is therefore called an endogenous pyrogen. The increased body temperature helps the body's immune system to fight infection. IL-1 is also important in the regulation of hematopoiesis. IL-1β production in peripheral tissue has also been associated with
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...]
(increased sensitivity to pain) associated with fever.
For the most part, these two forms of IL-1 bind to the same cellular
receptorIn biochemistry, a receptor is a protein molecule, embedded in either the plasma membrane or cytoplasm of a cell, to which a mobile signaling molecule may attach...
. This receptor is composed of two related, but non-identical, subunits that transmit intracellular signals via a pathway that is mostly shared with certain other receptors. These include the Toll family of innate immune receptors and the receptor for IL-18.
IL-1α is a
pleiotropicPleiotropy occurs when a single gene influences multiple phenotypic traits. Consequently, a new mutation in the gene may have an effect on some or all traits simultaneously...
cytokine involved in various immune responses,
inflammatory processesInflammation is the complex biological response of vascular tissues to harmful stimuli, such as pathogens, 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...
, and hematopoiesis. This cytokine is produced by many cell types but is only secreted by monocytes and macrophages. It is produced as a proprotein, which is
proteolyticallyProteolysis is the directed degradation of proteins by cellular enzymes called proteases or by intramolecular digestion.-Purposes:Proteolysis is used by the cell for several purposes...
processed by
calpainCalpains are a family of calcium-dependent, non-lysosomal cysteine proteases expressed ubiquitously in mammals and many other organisms. Calpains constitute the C2 family of protease clan CA in the MEROPS database. The calpain proteolytic system includes the calpain proteases, the small...
and released in a mechanism that is still not well studied. This gene and eight other interleukin 1 family genes form a cytokine gene cluster on chromosome 2. It has been suggested that the
polymorphismPolymorphism in biology occurs when two or more clearly different phenotypes exist in the same population of a species — in other words, the occurrence of more than one form or morph...
of these genes is associated with
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...
and
Alzheimer's diseaseAlzheimer's disease , also called Alzheimer disease, Senile Dementia of the Alzheimer Type or simply Alzheimer's, is the most common form of dementia. This incurable, degenerative, and terminal disease was first described by German psychiatrist and neuropathologist Alois Alzheimer in 1906 and was...
.
Additionally IL-1α is essential for maintenance of skin barrier function, especially with increasing age.
Structure of the IL-1 superfamily
IL-1α and IL-1β are produced as precursor peptides. In other words they are made as a long protein that is then processed to release a shorter, active molecule, which is called the mature protein. Mature IL-1β, for instance, is released from Pro-IL-1β following cleavage by a certain member of the
caspaseCaspases, or cysteine-aspartic proteases, are a family of cysteine proteases, which play essential roles in apoptosis , necrosis and inflammation....
family of proteins, called caspase-1 or the interleukin-1 converting
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...
(ICE). The 3-dimensional structure of the mature forms of each member of the human IL-1 superfamily is composed of 12-14 β-strands producing a barrel-shaped protein.
Receptor
See also Interleukin-1 receptorInterleukin-1 receptor is a cytokine receptor which binds interleukin 1. Two forms of the receptor exist. The type I receptor is primarily responsible for transmitting the inflammatory effects of interleukin-1 while type II receptors may act as a suppressor of IL-1 activity by competing for...
.
The receptors for interleukin 1 are:
- Interleukin 1 receptor, type I
Interleukin 1 receptor, type I also known as CD121a , is an interleukin receptor. IL1R1 also denotes its human gene.-Interactions:...
- Interleukin 1 receptor, type II
Interleukin 1 receptor, type II also known as CD121b is an interleukin receptor. IL1R2 also denotes its human gene.-External links:...