Regulatory effects of fever-range whole-body hyperthermia on the LPS-induced acute inflammatory response.

The thermal component of fever is one of the most poorly understood aspects of inflammation. To evaluate the role of fever-range hyperthermia on acute inflammation, BALB/c and C57BL/6 mice were exposed to mild, long-duration whole-body hyperthermia (WBH), and serum concentrations of tumor necrosis factor alpha (TNF-alpha), interleukin-6 (IL-6), IL-1beta, and the acute phase proteins (APPs) alpha1-acid glycoprotein and haptoglobin were analyzed. WBH alone did not affect serum concentrations of these cytokines or APPs when compared with controls. In contrast, when WBH was applied just after intraperitoneal administration of lipopolysaccharide (LPS), serum concentrations of TNF-alpha and IL-6 were greater than or equal to threefold higher in BALB/c mice compared with LPS-treated controls. LPS-induced IL-6 levels were also enhanced in WBH-treated C57BL/6 mice. However, APP levels were prolonged only in WBH-treated BALB/c mice. It is interesting that in vitro hyperthermia treatment of LPS-stimulated peritoneal cells resulted in decreased cytokine production compared with controls. These results suggest that fever-range hyperthermia regulates acute inflammation in a mouse strain-specific manner that is more complex than that observed in vitro.