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Updated: Aug 7, 2026

A Preclinical Model of Exertional Heat Stroke in Mice
Published on: July 1, 2021
Effect of caffeine supplementation on the extracellular heat shock protein 72 response to exercise
Martin Whitham1, Gary J Walker, Nicolette C Bishop
1School of Sport, Health and Exercise Sciences, University of Wales, Bangor, Holyhead Rd., Bangor LL57 2PZ, UK. m.whitham@bangor.ac.uk
Abstract:
The stimulus for the release of 72-kDa heat shock protein (HSP72) during exercise in humans is currently unclear. Recent evidence in an animal model is suggestive of an involvement of catecholamines. The present study, therefore, investigated the effect of caffeine supplementation, a known stimulator of sympathetic activity, on the extracellular (e)HSP72 response to prolonged exercise. Ten healthy male endurance-trained cyclists were recruited (age: 21 +/- 1 yr, maximum O(2) uptake 61.1 +/- 1.7 ml x kg(-1) x min(-1), mean +/- SE). Each subject was randomly assigned to ingest either 6 mg/kg body mass of caffeine (Caff) or placebo (Pla) 60 min before one of two 90-min bouts of cycling at 74 +/- 1% maximum O(2) uptake. Trials were performed at least 7 days apart in a counterbalanced design. Venous blood samples were collected by venepuncture at pretreatment, preexercise, postexercise, and 1 h postexercise. Serum caffeine and plasma catecholamines were determined using a spectrophotometric assay and high-performance liquid chromatography, respectively. Plasma HSP72 and cortisol were determined by ELISA. Serum caffeine concentrations were significantly increased throughout Caff, while no increases were detected in Pla. Caffeine supplementation and exercise was associated with a greater eHSP72 response than exercise alone (postexercise Caff 8.6 +/- 1.3 ng/ml; Pla 5.9 +/- 0.9 ng/ml). This greater eHSP72 response was associated with a greater epinephrine response to exercise in Caff. There was a significant increase in norepinephrine and cortisol, with no intertrial differences. The present data suggest that, in humans, catecholamines may be an important mediator of the exercise-induced increase in eHSP72 concentration.
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