Biology Reference
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must adapt its behavior so that it is optimized for overcoming the disease. If a sick
animal is exposed to danger, for example, it is still able to make the appropriate
behavioral response to enable it to avoid the danger. Thus, fear-motivated behaviors
can take precedence over sickness-motivated behaviors when necessary. Sick animals
are not completely incapacitated or debilitated, and are still able to express complex
behaviors and to evaluate accurately any situation to which they are exposed and to
deal with it in an appropriate manner. Once this has been done, they will re-engage
in recuperative behavior.
12.2.1 Cytokines and Body Temperature
Moderate increases in body temperature augment the immune response and are the
result of a rise in the hypothalamic thermal set point evoked by a change in neuronal
activity of the preoptic area. This effect is mediated by IL-1 and IL-6, which func-
tion as endogenous pyrogens. Mice deficient in either IL-1 or IL-6 are resistant to
turpentine-induced fever and do not demonstrate the increases in circulating prosta-
glanin E (PGE) 2 that are normally noted in wild-type mice. These pyrogenic cytok-
ines induce the expression of PGE 2 , which acts as the final mediator in the initiation
of fever. IL-6 is particularly important, as LPS (except at very high doses), IL-1,
and TNF- do not evoke fever in IL-6-deficient mice, although this effect can be
reversed by intracerebral administration of IL-6. Nevertheless, IL-6 knockout mice
still have normal circadian body temperature variations. Conversely, IL-10 (an anti-
inflammatory cytokine) inhibits the synthesis of pro-inflammatory cytokines and
IL-10-deficient mice have a markedly enhanced pyrogenic response to LPS.
The fever that occurs following infection is an important means whereby the host
combats infection. Fever increases the mobility and activity of neutrophils and the
production and activity of interferon, which is itself pyrogenic. IL-1, an important
initiator of the acute phase response, exerts a stimulatory effect on T lymphocytes,
which is enhanced at febrile temperatures. Finally, fever, coupled with a decrease in
plasma iron concentration, slows the rate of bacterial growth [26] . Reduced activity
and somnolence (see Section 12.2.2) enable energy conservation that allows the full
development of a fever that plays an essential role in recovery from infection. Thus, a
body temperature ranging from 38°C to 40°C potentiates immune-cell function while
diminishing the growth rate of numerous viral or bacterial pathogens. For example,
rabbits exposed to infection have an optimal survival rate when their body tempera-
ture increases by 2°C. A metabolic increase of 13% is required to raise body tem-
perature by 1°C, so it is not surprising that energetically expensive behaviors (such
as locomotor activity) are reduced, thereby minimizing heat loss.
12.2.2 Cytokines and Sleep
Increased fatigue and somnolence are common features of the acute phase response.
In animal models of infection, biphasic changes in non-REM sleep have been
reported, followed by prolonged decreases lasting for more than 24 hours. Sleep is
significant in host defense, and animals that exhibit enhanced sleep have fewer signs
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