Cytokines do not always elevate body temperature. Several peptides reduce the thermoregulatory set-point; these are known as endogenous cryogens. Putative endogenous cryogens include a-melanocyte-stimulating hormone, AVP, and several inhibitors of proinflammatory cytokines. In addition, tumor necrosis factor, normally considered a 'proinflammatory' cytokine, may also act as an endogenous cryogen. Such mediators may be functionally significant; for example, there is evidence that some of the action of salicylates, in addition to their inhibition of cyclo-oxygenase, may be partially mediated by release of endogenous AVP.
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