Exposure to febrile temperature upregulates expression of pyrogenic cytokines in endotoxin-challenged mice

Fever is a phylogenetically ancient response that is associated with improv ed survival in acute infections. In endothermic animals, fever is induced b y a set of pyrogenic cytokines [tumor necrosis factor-alpha (TNF-alpha), in terleukin (IL)-1, and IL-6] that are also essential for survival in acute i nfections. We studied the influence of core temperature on cytokine express ion using an anesthetized mouse model in which core temperature was adjuste d by immersion in water baths. We showed that raising core temperature from basal (36.5-37.5 degrees C) to febrile (39.5-40 degrees C) levels increase d peak plasma TNF-alpha and IL-6 levels by 4.1- and 2.7-fold, respectively, and changed the kinetics of IL-1 beta expression in response to lipopolysa ccharide challenge. TNF-alpha levels were increased predominantly in liver, IL-1 beta levels were higher in lung, and IL-6 levels were widely increase d in multiple organs in the warmer mice. This demonstrates that the thermal component of fever may directly contribute to shaping the host response by regulating the timing, magnitude, and tissue distribution of cytokine gene ration during the acute-phase response.