Objective: The physiological increase in body temperature following infection or LPS-induced acute inflammation is mediated by proinflammatory cytokines such as tumor necrosis factor (TNF)α, interleukin-6 (IL-6) and interleukin-1β (IL-1β). Macrophages that have been stimulated by infectious agents release these cytokines locally. But, once macrophages are activated, could the subsequent elevation in body temperature serve to dampen the inflammatory response? This research is designed to evaluate this question and in general, to identify the effects of experimental hyperthermia on the inflammatory reaction.

Methods: Peritoneal macrophages were activated by thioglycollate to study the thermal regulation of genes and proteins that are known to be associated with the function of macrophages in the inflammatory reaction. We incubated thioglycollate-elicited peritoneal macrophages from BALB/c mice for 6 h at 37 and 39.5ºC with or without LPS and IFN-γ, and then determined the concentration of proinflammatory cytokines in cell culture supernatants 16 h later by ELISA.

Results: We found that mild thermal stress treatment alone does not induce the proinflammatory cytokine production by peritoneal macrophages. However, heat-treated cells consistently produce lower levels of TNF-α after IFN-γ and LPS stimulation compared to 37 ºC. Our data also shows that in vitro hyperthermia-treated peritoneal cells from BALB/c and C57BL/6 mice produce lower levels of IL-1β and IL-6 after LPS stimulation compared with normothermic controls.

Conclusions: In vitro heat treatment of LPS-stimulated peritoneal macrophages results in decreased cytokine production compared with normothermic cells. These data may signify a novel role for thermal stress to down-regulate an ongoing inflammatory response. In terms of defining the underlying heat-sensitive mechanisms involved here, we are currently using Western blotting to measure expression levels of heat shock proteins and heat shock factors in thioglycollate-elicited peritoneal macrophages treated with mild thermal stress compared to normothermic cells. These results can help us to understand the regulatory effects of mild thermal stress in acute inflammatory response.
Supported by NIH P01 CAP14045 and ROI CA71599