The thermoregulatory consequences of heat stroke: Are cytokines involved?

The thermoregulatory changes induced by prolonged heat exposure consist of hyperthermia in response to direct heat exposure, and a biphasic response consisting of hypothermia followed by “fever”, which develops during long-term recovery. This review discusses the importance of these thermoregulatory responses for prediction of heat stroke morbidity and mortality and the potential role of endogenous cytokines in the regulation of these responses. Current data suggest that the magnitude and duration of hypothermia is directly related to severity of the heat insult, whereas “fever” is a biomarker of the systemic inflammatory response syndrome (SIRS) that ensues during heat stroke recovery. Correlation studies showing elevated cytokine concentrations in human and animal heat stroke models suggest an adverse role of these substances in heat-induced SIRS, although few neutralization studies have been conducted to support this hypothesis. Preliminary results from cytokine and cytokine receptor knockout mice suggest that cytokines may not be involved in the thermoregulatory responses to heat stroke, but in some cases appear to have a protective, permissive role for heat stroke survival.