Study on the Physiological Significance of Endotoxin in Heatstroke

摘要

Cytokines are signaling proteins that regulate immune system function. Though local inflammatory reactions mediated by TNF-alpha and IL-1beta are relatively benign, systemic release of these cytokines can result in vascular shock. It is through such an immune system mechanism that bacterial E upon entering the blood stream evokes vascular shock. E, TNF-alpha and IL-lbeta circulate in human heatstroke to suggest E release from a heat-damaged gut may stimulate cytokines that contribute to the vascular shock noted in heatstroke. However, when damaged tissue undergoes necrotic cell death, immune activation can occur with the release of cytokine. Thus, shock cytokines might be released by heat-induced tissue necrosis, even in the absence of E. To further define the physiological significance of E in heatstroke, this study determined if heat injury of HWB could induce a cytokine response in the absence of E. Using thermoelectric technology, HWB was exposed to temperature modulations that precisely replicated those associated with a 70% rat heatstroke mortality rate. Following heat stress, some HWB cultures were exposed to E at concentrations reported to circulate in human heatstroke, while others remained unexposed. In the presence or absence of prior heat stress, the presence of E stimulated inflammatory cytokine (TNF-a and IL-1beta) release, while in E's absence such cytokines were not generated. Similar findings were noted for IL-6, a cytokine noted for its modulatory effects on TNF metabolism. Relative to anti- inflammatory cytokines, heat stress and/or E had no effect on IL-1srII, while heat stress reduced E-mediated IL-1ra levels. Thus, some factor, like endotoxin was required to provoke HWB cytokine expression, which tended to support an etiological role for E in heatstroke cytokine responses. Moreover, the heat stress and E conditions that characterize heatstroke affected HWB cytokine metabolism to favor a pro-inflammatory environment.