Effects of Hypothermia and Hyperthermia on Cytokine Production by Cultured Human Mononuclear Phagocytes from Adults and Newborns

Abstract

We have shown previously that febrile range temperatures modify cytokine production by adult macrophages. In this study, we compared the effects of moderate hyperthermia and hypothermia on the kinetics of lipopolysaccharide (LPS)-induced cytokine expression in monocytes and macrophages of newborns and adults. During culture at 40°C, the initial rates of tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) secretion were preserved, but the duration of secretion was shorter than the duration at 37°C. TNF-α and IL1-β concentrations in 24-h 40°C culture supernatants were reduced 18%-50%. IL-6 concentration in 24-h 40°C cultures was reduced 26%-29% in all cells except adult macrophages. At 32°C, changes in early (2 h) and sustained (24 h) cytokine expression were reversed compared with those caused by hyperthermia. Culturing adult macrophages at 32°C blunted early secretion of TNF-α and IL-6 by 69% and 65%, respectively, and increased TNF-α concentration at 24 h by 48% compared with levels at 37°C. In adult monocytes cultured at 32°C, early IL-6 and IL-1β 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 prevent prolonged exposure to potentially cytotoxic cytokines. Hypothermia, on the other hand, may worsen outcome in infections by delaying and prolonging cytokine production.