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Sickness behavior
 
 
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Sickness behavior is a coordinated set of adaptive
Adaptation

Adaptation is the process, which takes place under natural selection, whereby an organism becomes better suited to its habitat. Also, the term may refer to some characteristic which stands out as being especially significant in the organism's survival....
  behavioral changes that develop in ill
Illness

Illness can be defined as a state of poor health.It is sometimes considered a synonym for disease. Others maintain that fine distinctions exist....
 individuals during the course of an infection
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 resources to multiply ....
.Hart, B. L. (1988) "Biological basis of the behavior of sick animals". Neurosci Biobehav Rev. 12: 123-137. They usually (but not necessarily)Kent, S., Bluthe, R. M., Dantzer, R., Hardwick, A. J., Kelley, K. W., Rothwell, N. J. Vannice, J.






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Sickness behavior is a coordinated set of adaptive
Adaptation

Adaptation is the process, which takes place under natural selection, whereby an organism becomes better suited to its habitat. Also, the term may refer to some characteristic which stands out as being especially significant in the organism's survival....
  behavioral changes that develop in ill
Illness

Illness can be defined as a state of poor health.It is sometimes considered a synonym for disease. Others maintain that fine distinctions exist....
 individuals during the course of an infection
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 resources to multiply ....
.Hart, B. L. (1988) "Biological basis of the behavior of sick animals". Neurosci Biobehav Rev. 12: 123-137. They usually (but not necessarily)Kent, S., Bluthe, R. M., Dantzer, R., Hardwick, A. J., Kelley, K. W., Rothwell, N. J. Vannice, J. L. (1992) "Different receptor mechanisms mediate the pyrogenic and behavioral effects of interleukin 1". Proc Natl Acad Sci U S A. 89: 9117-9120. accompany fever
Fever

Fever is a frequent medical sign that describes an increase in internal body temperature to levels above normal. Fever is most accurately characterized as a temporary elevation in the body's thermoregulatory set-point, usually by about 1?2 ?C ....
 and aid survival. Such illness responses include lethargy, depression
Depression (mood)

In the fields of psychology and psychiatry, the terms depression or depressed refer to sadness and other related emotions and behaviours. It can be thought of as either a disease or a syndrome....
, anorexia
Anorexia (symptom)

Anorexia is the decreased sensation of appetite. While the term in non-scientific publications is often used interchangeably with anorexia nervosa, many possible causes exist for a decreased appetite, some of which may be harmless, while others indicate a serious clinical condition, or pose a significant risk....
,Exton, M. S. (1997) "Infection-induced anorexia: active host defence strategy". Appetite. 29: 369-383. sleepiness,Mullington, J., Korth, C., Hermann, D. M., Orth, A., Galanos, C., Holsboer, F. Pollmacher, T. (2000) "". Am J Physiol Regul Integr Comp Physiol. 278: R947-955 hyperalgesia
Hyperalgesia

Hyperalgesia 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 evolutionary medicine response to infection.Hart, B....
,Maier, S. F., Wiertelak, E. P., Martin, D. Watkins, L. R. (1993) "Interleukin-1 mediates the behavioral hyperalgesia produced by lithium chloride and endotoxin". Brain Res. 623: 321-324. reduction in grooming
Personal grooming

File:Cygnus atratus preening.jpgPersonal grooming is the art of cleaning, grooming, and maintaining parts of the body. In animals, it is a species-typical behavior that is controlled by Biological neural network in the brain....
Dantzer, R. Kelley, K. W. (2007) "Twenty years of research on cytokine-induced sickness behavior". Brain Behav Immun. 21: 153-160 and failure to concentrate
Attention

Attention is the cognitive process of selectively concentrating on one aspect of the environment while ignoring other things. Examples include listening carefully to what someone is saying while ignoring other conversations in a room or listening to a cell phone conversation while driving a car....
.Kelley, K. W., Bluthe, R. M., Dantzer, R., Zhou, J. H., Shen, W. H., Johnson, R. W. Broussard, S. R. (2003) "Cytokine-induced sickness behavior". Brain Behav Immun. 17 Suppl 1: S112-118. Sickness behavior is a motivational state
Motivation

Motivation is the set of reasons that determines one to engage in a particular behavior. The term is generally used for human motivation but, theoretically, it can be used to describe the causes for animal behavior as well....
 that reorganizes the organism’s priorities to cope with infectious pathogens.Johnson, R. (2002) "The concept of sickness behavior: a brief chronological account of four key discoveries". Veterinary Immunology and Immunopathology. 87: 443-450 It has been suggested as relevant to understanding depression
Depression (mood)

In the fields of psychology and psychiatry, the terms depression or depressed refer to sadness and other related emotions and behaviours. It can be thought of as either a disease or a syndrome....
, and some aspects of the suffering that occurs in cancer
Cancer

Cancer is a class of diseases in which a group of cell display uncontrolled growth , invasion , and sometimes metastasis . These three malignant properties of cancers differentiate them from benign tumors, which are self-limited, do not invade or metastasize....
.

History

Sick animals have long been recognized by farmers as having different behavior. Initially it was thought that this was due to physical weakness that resulted from diverting energy from the body processes needed to fight infection. However, in the 1960s, it was shown that animals produced a blood carried ‘‘factor X’’ that acted upon the brain to cause this such sickness behavior.Holmes, J. E. Miller, N. E. (1963) "Effects of Bacterial Endotoxin on Water Intake, Food Intake, and Body Temperature in the Albino Rat". J Exp Med. 118: 649-658 In 1987, Benjamin L. Hart brought together a variety of research findings that argued for them being survival adaptations
Evolutionary medicine

Evolutionary medicine or Darwinian medicine is the application of modern evolution to understanding health and disease. It provides a complementary scientific approach to the present Mechanism_ that dominate medical science, and particularly modern medical education....
 that if prevented would disadvantage an animal’s ability to fight infection. In the 1980s, the blood borne factor was shown to be proinflammatory cytokines produced by activated leukocytes in the immune system
Immune system

An immune system is a collection of biological processes within an organism that protects against disease by identifying and killing pathogens and tumour cells....
 in response to lipopolysaccharides (a cell wall component of Gram-negative bacteria). These cytockines acted by various humeral and nerve
Nerve

A nerve is an enclosed, cable-like bundle of Peripheral nervous system axons . A nerve provides a common pathway for the electrochemical nerve impulses that are transmitted along each of the axons....
 routes upon the hypothalmus and other areas of the brain. Further research showed that the brain can also learn to control the various components of sickness behavior independently of immune activation.

General advantage


Sickness behavior in its different aspects causes an animal to limit its movement and so reduce its energy expenditure allowing this to be diverted to mobilize the fever response which involves raising body temperature. This also limits an animal’s exposure to predators while it is cognitively and physically impaired.

Specific advantages

The individual components of sickness behavior have specific individual advantages. Anorexia limits food ingestion and therefore reduces the availability of iron
Iron deficiency

Iron deficiency may refer to:*Iron deficiency *Iron deficiency ...
 and zinc
Zinc deficiency

Zinc deficiency also known as hypozincemia is a condition where insufficient zinc is available for metabolic needs. Zinc deficiency, at least in rats, can be induced by ingestion of histidine....
 in the gut (and from gut absorption). Iron and zinc may aid bacterial reproduction so their reduction is useful during sickness.Kluger, M. J. Rothenburg, B. A. (1979) "Fever and reduced iron: their interaction as a host defense response to bacterial infection". Science. 203: 374-376. Plasma concentrations of iron and zinc are lowered for this anti-bacterial reason in fever.Weinberg, E. D. (1984) "Iron withholding: a defense against infection and neoplasia". Physiol Rev. 64: 65-102. Lowered threshold for pain
Pain threshold

In scientific and medical literature the term pain threshold indicates the minimum stimulus which elicits pain and is clearly differentiated from the term pain tolerance which indicates the degree of pain which a subject can tolerate before experiencing physical or emotional impairment and involves a measurement of a subject's response t...
 ensures that an animal is attentive that it does not place pressure on injured and inflamed tissues that might disrupt their healing. Reduced grooming is adaptive since it reduces water loss.

Immune control

Lipopolysaccharides trigger the immune system
Immune system

An immune system is a collection of biological processes within an organism that protects against disease by identifying and killing pathogens and tumour cells....
 to produce proinflammatory cytokines
Proinflammatory cytokine

A proinflammatory cytokine is a cytokine which promotes systemic inflammation.Examples include IL-1 and TNF alpha.References...
 IL-1
IL-1

IL-1 may refer to:* Interleukin 1, a protein* Illinois' 1st congressional district* Illinois Route 1* Building 1 of Infinite Loop , the Headquarters of Apple Inc....
, IL-6, and tumor necrosis factor
Tumor necrosis factor

Tumor necrosis factor is a cytokine involved in systemic inflammation and is a member of a group of cytokines that stimulate the acute phase reaction....
 (TNF).Kent, S., Bluthe, R. M., Dantzer, R., Hardwick, A. J., Kelley, K. W., Rothwell, N. J. Vannice, J. L. (1992) "Different receptor mechanisms mediate the pyrogenic and behavioral effects of interleukin 1". Proc Natl Acad Sci U S A. 89: 9117-9120 These peripherally released cytokines act on the brain via a fast transmission pathway involving primary input through the vegus nerves,Goehler, L. E., Gaykema, R. P., Nguyen, K. T., Lee, J. E., Tilders, F. J., Maier, S. F. Watkins, L. R. (1999) "Interleukin-1beta in immune cells of the abdominal vagus nerve: a link between the immune and nervous systems?" J Neurosci. 19: 2799-2806 and a slow transmission pathway involving cytokines originating from the choroid plexus
Choroid plexus

The choroid plexus is the area on the ventricle s of the brain where cerebrospinal fluid is produced by modified ependymal cells....
 and circumventricular organs
Circumventricular organs

Circumventricular organs are so named because they are positioned at distinct sites around the margin of the ventricular system of the brain. They are among the few sites in the brain which have an incomplete blood-brain barrier....
 and diffusing into the brain parenchyma by volume transmission
Neuromodulation

In neuroscience, neuromodulation is the process in which several classes of neurotransmitters in the nervous system regulate diverse populations of neurons , as opposed to direct synapse in which one presynaptic neuron directly influences a postsynaptic partner , neuromodulatory transmitters secreted by a small group of neurons diffuse throug...
.Konsman, J. P., Kelley, K. Dantzer, R. (1999) "Temporal and spatial relationships between lipopolysaccharide-induced expression of Fos, interleukin-1beta and inducible nitric oxide synthase in rat brain". Neuroscience. 89: 535-548 Peripheral cytokines may enter directly the brain.Banks, W. A., Kastin, A. J. Gutierrez, E. G. (1994) "Penetration of interleukin-6 across the murine blood-brain barrier". Neurosci Lett. 179: 53-56 They may also induce the expression of other cytokines in the brain that cause sickness behavior.Ban, E., Haour, F. Lenstra, R. (1992) "Brain interleukin 1 gene expression induced by peripheral lipopolysaccharide administration". Cytokine. 4: 48-54

Behavioral conditioning


The components of sickness behavior can be learned by conditional association
Classical conditioning

Classical Conditioning is a form of associative learning that was first demonstrated by Ivan Pavlov . The typical procedure for inducing classical conditioning involves presentations of a neutral stimulus along with a stimulus of some significance....
. For example, if a saccharin
Saccharin

Saccharin is an artificial sweetener. The basic substance, benzoic sulfinide, has effectively no food energy and is much sweeter than sucrose, but has an unpleasant bitter or metallic aftertaste, especially at high concentrations....
 solution is given with a chemical that triggers a particular aspect of sickness behavior, on later occasions the saccharin solution will trigger it by itself.Exton, M. S., Bull, D. F. King, M. G. (1995) "Behavioral conditioning of lipopolysaccharide-induced anorexia". Physiol Behav. 57: 401-405.

Depression


It has been proposed that major depressive disorder is near-identical with sickness behavior, so raising the possibility that it is a maladaptive manifestation of sickness behavior due to abnormalities in circulating cytokines.Charlton, B. G. (2000) "The malaise theory of depression: major depressive disorder is sickness behavior and antidepressants are analgesic". Med Hypotheses. 54: 126-130 Maes, M. (2008) "The cytokine hypothesis of depression: inflammation, oxidative & nitrosative stress (IO&NS) and leaky gut as new targets for adjunctive treatments in depression". Neuro Endocrinol Lett. 29: 287-291

Cancer side effect


In cancer, both the disease and the chemotherapy
Chemotherapy

Chemotherapy, in its most general sense, refers to treatment of disease by chemicals that kill cells, specifically those of micro-organisms or cancer....
 treatment can cause proinflammatory cytokine release which can cause sickness behavior as a side effect
Adverse effect (medicine)

In medicine, an adverse effect is a harmful and undesired effect resulting from a medication or other intervention such as chemotherapy or surgery....
.Cleeland, C. S., Bennett, G. J., Dantzer, R., Dougherty, P. M., Dunn, A. J., Meyers, C. A., Miller, A. H., Payne, R., Reuben, J. M., Wang, X. S. Lee, B. N. (2003) "Are the symptoms of cancer and cancer treatment due to a shared biologic mechanism? A cytokine-immunologic model of cancer symptoms". Cancer. 97: 2919-2925

See also


  • Evolutionary medicine
    Evolutionary medicine

    Evolutionary medicine or Darwinian medicine is the application of modern evolution to understanding health and disease. It provides a complementary scientific approach to the present Mechanism_ that dominate medical science, and particularly modern medical education....
  • Proinflammatory cytokines
    Proinflammatory cytokine

    A proinflammatory cytokine is a cytokine which promotes systemic inflammation.Examples include IL-1 and TNF alpha.References...