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 degrees C and 37.6 +/- 0.8 degrees C in exertional heatstroke and exertional controls, respectively. Significantly, plasma cytokines including interleukin (IL)-1beta (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-gamma 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.