Role of circulating cytokines and chemokines in exertional heatstroke

Objective: The interplay between inflammatory and anti-inflammatory cytokines, as well as chemokines, has not been well explored in exertional heatstroke. Design: Prospective, observational study. Patients: Seventeen military recruits who developed exertional heatstroke and 17 exertional controls who did not develop exertional heatstroke during the same training exercises. Setting: University teaching hospital. Measurements and Main Results: The severity of exertional heatstroke was evaluated using a Simplified Acute Physiology Score. Plasma cytokines and chemokines were determined using enzyme-linked immunosorbent assay kits. Body temperatures were 41.2 ± 1.2°C and 37.6 ± 0.8°C in exertional heatstroke and exertional controls, respectively. Significantly, plasma cytokines including interleukin (IL)-1β (3.1 ± 1.6 vs. 1.2 ± 0.8 pg/mL; p <.05), tumor necrosis factor alpha (4.9 ± 4.1 vs. 1.2 ± 2.4 pg/mL; p <.05), IL-6 (15.8 ± 3.2 vs. 1.2 ± 1.2 pg/mL; p <.01), interferon gamma (7.3 ± 4.9 vs. 2.4 ± 4.1 pg/mL; p <.01), IL-2 receptor (1568 ± 643 vs. 610 ± 214 pg/mL; p <.01), IL-4 (2.5 ± 1.2 vs. 1.2 ± 0.8 pg/mL; p <.05), and IL-10 (12.9 ± 9.4 vs. 2.5 ± 4.9 pg/mL; p <.01) and serum chemokines IL-8 (84.2 ± 79.9 vs. 10.4 ± 3.2 pg/mL; p <.01), monocyte chemoattractant protein 1 (959 ± 589 vs. 158 ± 217 pg/mL; p <.01), and RANTES (12464 ± 10505 vs. 5570 ± 2894 pg/mL; p <.01) were elevated in exertional heatstroke compared with exertional controls. Among cytokines, IL-6, interferon gamma, and IL-2 receptor were positively correlated with Simplified Acute Physiology Score (r = .573, p <.01; r = .625, p <.01; and r = .56, p <.05, respectively). Among chemokines, only serum monocyte chemoattractant protein 1 was positively correlated with Simplified Acute Physiology Score (r = .78, p <.001). There was no correlation between either cytokines or chemokines and body temperature. Conclusions: Proinflammatory cytokines IL-1beta;, tumor necrosis factor alpha, IL-6; T helper 1 cytokines INF-γ and IL-2 receptor; and chemokines IL-8, monocyte chemoattractant protein 1, and RANTES are increased in patients with exertional heatstroke. T helper 2 cytokines may play a role as anti-inflammatory cytokines. IL-6, interferon gamma, IL-2 receptor, and monocyte chemoattractant protein 1 may serve as prognostic indicators of disease severity in exertional heatstroke.