Cytokine induction during exertional hyperthermia is abolished by core temperature clamping: neuroendocrine regulatory mechanisms

The immunomodulatory effects of physiological temperature change remain poorly understood and inter-relationships between changes in core temperature, stress hormones and cytokines during exertional hyperthermia are not well established. This experimental study was designed to examine how cytokine (tumour necrosis factor (TNF)-alpha, interleukin (IL)-6, IL-12 and IL-1ra (receptor antagonist)) and hormone (epinephrine (Epi), norepinephrine (NE), growth hormone (GH) and cortisol (CORT)) responses are modified when the exercise-induced rise in core temperature is attenuated or exacerbated by immersion in a water bath. Ten men ((mean +/- SD) age: 26.9 +/- 5.7 years; height 1.75 +/- 0.07 m; body mass 76.0 +/- 10.9 kg; (V) over dot O-2peak: 48.0 +/- 12.4 mL kg(-1) min(-1)) completed two 40-min cycle ergometer exercise trials at 65% (V) over dot O-2peak while immersed to mid-chest. Rectal temperature (T-re) peaked at 39.1 +/- 0.03 and 37.5 +/- 0.13degreesC during the hot (39degreesC) and cold (18degreesC) conditions, respectively. Blood samples were collected before, during (20- and 40-min) and after (30- and 120-min) exercise. Increases in circulating NE (> 350%), Epi (> 500%), GH (>900%), IL-12 (> 150%) and TNF-alpha (>90%) were greatest after 40-min exercise in the heat. Substantial elevations of CORT (80%), IL-1ra (150%) and IL-6 (>400%) did not occur until after exercise was complete. Core temperature clamping decreased the rise in circulating stress hormone concentrations and abolished increases in plasma cytokine concentrations. These findings suggest that exercise-associated elevations of T-re mediate increases of circulating stress hormones, which subsequently contribute to induction of circulating cytokine release.