Sickness behavior

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Ancher, Michael, "The Sick Girl", 1882, Statens Museum for Kunst.

Sickness behavior is a coordinated set of adaptive behavioral changes that develop in ill individuals during the course of an infection.[1] They usually (but not necessarily)[2] accompany fever and aid survival. Such illness responses include lethargy, depression, anxiety, loss of appetite,[3][4] sleepiness,[5] hyperalgesia,[6] reduction in grooming[1][7] and failure to concentrate.[8] Sickness behavior is a motivational state that reorganizes the organism's priorities to cope with infectious pathogens.[8][9] It has been suggested as relevant to understanding depression, and some aspects of the suffering that occurs in cancer.

History[edit]

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 to 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 sickness behavior.[10][11] In 1987, Benjamin L. Hart brought together a variety of research findings that argued for them being survival adaptations 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 in response to lipopolysaccharides (a cell wall component of Gram-negative bacteria). These cytokines acted by various humoral and nerve routes upon the hypothalamus 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.[citation needed]

Advantages[edit]

General advantage[edit]

Sickness behavior in its different aspects causes an animal to limit its movement; the metabolic energy not expended in activity is diverted to the fever responses, which involves raising body temperature.[1] This also limits an animal’s exposure to predators while it is cognitively and physically impaired.[1]

Specific advantages[edit]

The individual components of sickness behavior have specific individual advantages. Anorexia limits food ingestion and therefore reduces the availability of iron in the gut (and from gut absorption). Iron may aid bacterial reproduction, so its reduction is useful during sickness.[12] Plasma concentrations of iron are lowered for this anti-bacterial reason in fever.[13] Lowered threshold for pain ensures that an animal is attentive that it does not place pressure on injured and inflamed tissues that might disrupt their healing.[1] Reduced grooming is adaptive since it reduces water loss.[1]

Immune control[edit]

Lipopolysaccharides trigger the immune system to produce proinflammatory cytokines IL-1, IL-6, and tumor necrosis factor (TNF).[2] These peripherally released cytokines act on the brain via a fast transmission pathway involving primary input through the vagus nerves,[14][15] and a slow transmission pathway involving cytokines originating from the choroid plexus and circumventricular organs and diffusing into the brain parenchyma by volume transmission.[16] Peripheral cytokines may enter the brain directly.[17][18] They may also induce the expression of other cytokines in the brain that cause sickness behavior.[19][20] Acute psychosocial stress enhances the ability of an immune response to trigger both inflammation and behavioral sickness.[21]

Behavioral conditioning[edit]

The components of sickness behavior can be learned by conditional association. For example, if a saccharin 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.[22][23]

Medical conditions[edit]

Depression[edit]

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.[24][25][26][27] Moreover, chronic, but not acute treatment with antidepressant drugs was found to attenuate sickness behavior symptoms in rodents.[28] The mood effects caused by interleukin-6 following an immune response have been linked to increased activity within the subgenual anterior cingulate cortex,[29] an area involved in the etiology of depression.[30] Inflammation-associated mood change can also produce a reduction in the functional connectivity of this part of the brain to the amygdala, medial prefrontal cortex, nucleus accumbens, and superior temporal sulcus.[29]

Cancer side effect[edit]

In cancer, both the disease and the chemotherapy treatment can cause proinflammatory cytokine release which can cause sickness behavior as a side effect.[31][32]

See also[edit]

References[edit]

  1. ^ a b c d e f Hart, BL (1988). "Biological basis of the behavior of sick animals". Neuroscience and biobehavioral reviews 12 (2): 123–37. doi:10.1016/S0149-7634(88)80004-6. PMID 3050629.  edit
  2. ^ a b 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". Proceedings of the National Academy of Sciences of the United States of America 89 (19): 9117–9120. doi:10.1073/pnas.89.19.9117. PMC 50076. PMID 1409612.  edit
  3. ^ Exton, M. S. (1997). "Infection-Induced Anorexia: Active Host Defence Strategy". Appetite 29 (3): 369–383. doi:10.1006/appe.1997.0116. PMID 9468766.  edit
  4. ^ Murray, M. J.; Murray, A. B. (1979). "Anorexia of infection as a mechanism of host defense". The American journal of clinical nutrition 32 (3): 593–596. PMID 283688.  edit
  5. ^ Mullington, J.; Korth, C.; Hermann, D. M.; Orth, A.; Galanos, C.; Holsboer, F.; Pollmächer, T. (2000). "Dose-dependent effects of endotoxin on human sleep". American journal of physiology. Regulatory, integrative and comparative physiology 278 (4): R947–R955. PMID 10749783.  edit
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  8. ^ a b Kelley, KW; Bluthé, RM; Dantzer, R; Zhou, JH; Shen, WH; Johnson, RW; Broussard, SR (2003). "Cytokine-induced sickness behavior". Brain, behavior, and immunity. 17 Suppl 1: S112–8. doi:10.1016/S0889-1591(02)00077-6. PMID 12615196.  edit
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  13. ^ Weinberg, E. D. (1984). "Iron withholding: A defense against infection and neoplasia". Physiological reviews 64 (1): 65–102. PMID 6420813.  edit
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  19. ^ Ban, E.; Haour, F.; Lenstra, R. (1992). "Brain interleukin 1 gene expression induced by peripheral lipopolysaccharide administration". Cytokine 4 (1): 48–54. doi:10.1016/1043-4666(92)90036-Q. PMID 1535519.  edit
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