ELEVATED PYROGENIC CYTOKINES IN HEATSTROKE

Study Objectives: Heatstroke, characterized by hyperthermia and neurol ogic abnormalities, can cause shock, adult respiratory distress syndro me, and multiorgan failure culminating in death. The mediation of meta bolic changes and tissue damage is not fully understood. Recent eviden ce suggests the involvement of endotoxin, tumor necrosis factor alpha (TNF-alpha), and interleukin 1 alpha (IL-1alpha) and we hypothesized t hat other pyrogenic cytokines may be implicated.Design: Prospective an alysis. Setting: Heatstroke Center in Makkah (Mecca), Saudi Arabia. Me asurements and Results: We measured plasma IL-1beta, IL-6, and interfe ron gamma (INF-gamma) concentrations by enzyme-linked immunosorbent as say in 28 heatstroke patients at the time of hospital admission (preco oling) and after complete cooling (postcooling), and in 10 normal cont rol subjects. We measured C-reactive protein (CRP) as a marker of acut e phase response and calculated severity of illness using the simplifi ed acute physiology score. Twenty-five male and 3 female subjects had mean (+/- SEM) rectal temperature of 41.2 +/- 0.2-degrees-C. IL-6, IL- 1beta, and INF-gamma concentrations were elevated in 100 percent, 39 p ercent, and 50 percent of patients to (mean +/- SEM) 220 +/- 44 pg/ml, 42 +/- 14 pg/ml, and 1,180 +/- 879 pg/ml, respectively (normal contro l values: < 3.5 pg/ml, < 4.5 pg/ml, < 20 pg/ml). The CRP value was ele vated in 72 percent of patients to 152 +/- 40 mg/L (control value: 0 t o 17 mg/L). The IL-6 concentrations correlated with severity of illnes s (r=0.516, p=0.03); two patients with the highest concentrations died . There was no significant correlation between circulating levels of I L-6, IL-1beta, INF-gamma, and temperature, or between IL-6, IL-1beta, and CRP. Postcooling, IL-6, and IL-1beta were still above normal contr ol values; INF-gamma could be detected in one patient only. Conclusion : Our findings of elevated circulating IL-6, IL-1beta, and INF-gamma i n the presence of acute phase response, and correlation with severity of illness, suggest that these cytokines have a role in the pathogenes is of heatstroke, which could lead to new therapeutic strategies.