Elevated pyrogenic cytokines in heatstroke

Abstract

Study Objectives: Heatstroke, characterized by hyperthermia and neurologic abnormalities, can cause shock, adult respiratory distress syndrome, and multiorgan failure culminating in death. The mediation of metabolic changes and tissue damage is not fully understood. Recent evidence suggests the involvement of endotoxin, tumor necrosis factor alpha (TNF-α), and interleukin 1 alpha (IL-1α) and we hypothesized that other pyrogenic cytokines may be implicated. Design: Prospective analysis. Setting: Heatstroke Center in Makkah (Mecca), Saudi Arabia. Measurements and Results: We measured plasma IL-1β, IL-6; and interferon gamma (INF-γ) concentrations by enzyme-linked immunosorbent assay in 28 heatstroke patients at the time of hospital admission (precooling) and after complete cooling (postcooling), and in 10 normal control subjects. We measured C-reactive protein (CRP) as a marker of acute phase response and calculated severity of illness using the simplified acute physiology score. Twenty-five male and 3 female subjects had mean (±SEM) rectal temperature of 41.2±0.2°C. IL-6, IL-1β, and INF-γ concentrations were elevated in 100 percent, 39 percent, and 50 percent of patients to (mean±SEM) 220±44 pg/ml, 42±14 pg/ml, and 1,180±879 pg/ml, respectively (normal control values: <3.5 pg/ml, <4.5 pg/ml, <20 pg/ml). The CRP value was elevated in 72 percent of patients to 152±40 mg/L (control value: 0 to 17 mg/L). The IL-6 concentrations correlated with severity of illness (r=0.516, p=0.03); two patients with the highest concentrations died. There was no significant correlation between circulating levels of IL-6, IL- 1β, INF-γ, and temperature, or between IL-6, IL-1β, and CRP. Postcooling, IL-6, and IL-1β were still above normal control values; INF-γ could be detected in one patient only. Conclusion: Our findings of elevated circulating IL-6, IL-1β, and INF-γ in the presence of acute phase response, and correlation with severity of illness, suggest that these cytokines have a role in the pathogenesis of heatstroke, which could lead to new therapeutic strategies.