Febrile core temperature is essential for optimal host defense in bacterial peritonitis

Fever, a nonspecific acute-phase response, has been associated with improve d survival and shortened disease duration in infections, but the mechanisms of these beneficial responses are poorly understood. We previously reporte d that increasing core temperature of bacterial endotoxin (LPS)-challenged mice to the normal febrile range modified expression of tumor necrosis fact or alpha (TNF-alpha), interleukin 1 beta (IL-1 beta), and IL-6, three cytok ines critical to mounting an initial defense against microbial pathogens, b ut survival was not improved in the warmer animals. We speculated that our inability to show a survival benefit of optimized cytokine expression in th e warmer animals reflected our use of LPS, a nonreplicating agonist, rather than an infection with viable pathogens. The objective of this study was t o determine if increasing murine core temperature altered cytokine expressi on and improved survival in an experimental bacterial peritonitis model. We showed that housing mice at 35.5 degrees C rather than 23 degrees C increa sed core temperature from 36.5 to 37.5 degrees C to 39.2 to 39.7 degrees C, suppressed plasma TNF-alpha expression for the initial 48 h, delayed gamma interferon expression, improved survival, and reduced the bacterial load i n mice infected with Klebsiella pneumoniae peritonitis. We showed that the reduced bacterial load was not caused by a direct effect on bacterial proli feration and probably reflected enhanced host defense. These data suggest t hat the increase in core temperature that occurs during bacterial infection s is essential for optimal antimicrobial host defense.