Plasma heat shock protein-70 response to acute prolonged exercise: a systematic review, meta-analysis, and meta-regression

Extracellular heat shock protein 70 (HSP70) acts as a damage-associated molecular pattern, or "danger signal" for the immune system. Acute prolonged exercise evokes various physiological stresses that can stimulate the release of extracellular HSP70. However, exercise-induced extracellular HSP70 responses are inconsistent in human studies. Therefore, the purpose of this meta-analysis and meta-regression was to systematically evaluate the effect of exercise on plasma HSP70 expression and to determine the exercise-associated factors contributing to plasma HSP70 response. Data were extracted from 26 experimental trials from 13 studies, including 154 participants, in which plasma HSP70 was measured before and after prolonged, continuous running or cycling exercise at a fixed intensity relative to V̇o_2max. Meta-analysis was performed to determine the raw mean difference (MD) between post- and pre-exercise HSP70 concentration. Meta-regression was performed to establish the moderating effects of V̇o_2max, exercise intensity, duration, modality, environmental temperature, humidity, and hypoxia on the plasma HSP70 response. There was a significant effect of exercise on plasma HSP70 concentration (MD = 0.73 ng·mL^-1, 95% CI [0.13, 1.34], <i>P</i> = 0.02). Meta-regression explained ∼57.1% of variation in exercise-induced change in plasma HSP70 concentration (marginal <i>R²</i> = 0.571). The V̇o_2max (β = 0.51, 95% CI [0.03, 1.00]), exercise duration (β = 0.43, 95% CI [0.21, 0.65]), intensity (β = 0.40, 95% CI [0.08, 0.73]), and environmental temperature (β = 0.27, 95% CI [0.10, 0.43]) explained variation in the plasma HSP70 response. These data contribute to our understanding of the factors that modulate the plasma HSP70 response to acute prolonged exercise.