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Abstract

Introduction: Increased levels of circulating endotoxin have been identified in patients with heatstroke; however, the exact mechanisms of heatstroke are not fully elucidated. We questioned whether susceptibility to the circulating endotoxin is increased in pathogenesis of heatstroke. Hypothesis: We hypothesized that exposure to heat environment increases susceptibility to lipopolysaccharide (LPS) in mice. Methods: Male 8- to 10- week-old C3H/HeN mice were divided into two groups (n = 25/group). The animals were anesthetized and placed in heat environment (42 degrees C) or in normal environment (23 degrees C) for one hour. Then, mice were injected intraperitonially with 50, 100, 200, 400 or 800 mcg of LPS (n = 5/subgroup). All mice were housed at normal ambient temperature (23 degrees C) after injection. Mortality was recorded for up to 5 days after heat exposure and the lethal dose (LD50) of LPS was determined in each group. We then measured changes of serum cytokine levels after LPS injection. After one hour exposure to heat (42 degrees C), LPS (141 mcg/body) was injected intraperitonially (H group). Control group (C group) was given the same doses of LPS without heat stress (23 degrees C). Blood samples were taken at 1, 2, 6, 12 hours after injection for determination of TNF-alpha levels, at 2, 6, 12, 24, 36, 48 hours for IL-6 levels and at 2, 6, 12, 24 hours for IL-10 levels. Results: Groups of mice injected 200 mcg or 400 mcg of LPS after heat stress showed significantly higher mortality compared to the control group. LD50 of LPS was determined 141 mcg in the heat exposed group, whereas 258 mcg in the control group. TNF-alpha level of H group was significantly higher than that of C group at 1 and 2 hours after LPS injection. IL-6 levels rapidly elevated after LPS injection in both groups. Elevated IL-6 level was sustained 24 h and 36 h after LPS injection in H group whereas IL-6 level declined earlier in C group. Difference of serum IL-10 levels between C group and H group was not statistically significant. Conclusions: These data demonstrate that increased susceptibility is related to mortality of heatstroke and enhanced cytokine production plays an important role in the pathophysiology of heatstroke.