Effects of hypothermia and hyperthermia on cytokine production by culturedhuman mononuclear phagocytes from adults and newborns

We have shown previously that febrile range temperatures modify cytokine pr oduction by adult macrophages. In this study, we compared the effects of mo derate hyperthermia and hypothermia on the kinetics of lipopolysaccharide ( LPS)-induced cytokine expression in monocytes and macrophages of newborns a nd adults. During culture at 40 degreesC, the initial rates of tumor necros is factor-alpha (TNF-alpha) and interleukin-1 beta (IL-1 beta) secretion we re preserved, but the duration of secretion was shorter than the duration a t 37 degreesC, TNF-alpha and IL-1 beta concentrations in 24-h 40 degreesC c ulture supernatants were reduced 18%-50%. IL-6 concentration in 24-h 40 deg reesC cultures was reduced 26%-29% in all cells except adult macrophages. A t 32 degreesC, changes in early (2 h) and sustained (24 h) cytokine express ion were reversed compared with those caused by hyperthermia. Culturing adu lt macrophages at 32 degreesC blunted early secretion of TNF-alpha and IL-6 by 69% and 65%, respectively, and increased TNF-alpha concentration at 24 h by 48% compared with levels at 37 degreesC. In adult monocytes cultured a t 32 degreesC, early IL-6 and IL-1 beta secretion was decreased 64% and 51% , respectively. We speculate that the burst/suppression cytokine profile at febrile temperatures might enhance early activation of host defenses and p revent prolonged exposure to potentially cytotoxic cytokines, Hypothermia, on the other hand, may worsen outcome in infections by delaying and prolong ing cytokine production.