Exertional vs. Passive Heat Stroke: Altered Time Course of Cytokine Expression in Plasma and Skeletal Muscle

Abstract

Exertional heat stroke (EHS) is a unique model where hyperthermia, exhaustive exercise, and other signals place simultaneous demands on the innate immune system. We hypothesized that when heat was superimposed on exercise there would be an exaggerated stress response due to the cumulative effect of these factors. To explore this, we determined cytokine protein expression in plasma and changes in skeletal muscle gene expression post EHS, passive heat stroke (PHS), exercise sham controls (EXC), and exhaustive exercise (EE) and compared these to naïve controls (NC). Gene expression was evaluated using qRT‐PCR in the diaphragm (DIA), soleus (SOL), and gastrocnemius (GASTROC) at 0.5, 3, 24, and 96 hrs after treatment. Plasma cytokine proteins were determined using Luminex. In EHS and in EXC, peak plasma IL‐6 was observed at 0.5 hr recovery; by 3 hrs it was not different from NC. Contrastingly, following PHS, IL‐6 reached a peak at 3 hrs. IL‐10 was also significantly elevated at 3 hrs in PHS, whereas in EXC and EHS there were no elevations. In EHS, IL‐6 mRNA in the SOL and DIA was increased 0.5 hr post treatment while IL‐10 was only increased in the DIA. In PHS, 30 min post, IL‐6 and IL‐10 mRNA were greatly elevated. Importantly, 30 min after EE or EXC, IL‐6 and IL‐10 mRNA in SOL and GASTROC were significantly suppressed relative to NC. SOCS3 (a downstream response to IL‐6 and IL‐10 receptor activation via JAK/STAT3) was measured as a possible mechanism for suppression of IL‐6 and IL‐10. In EHS SOCS3 was elevated at 30 min in SOL, implying cytokine signaling events began early during exercise or heat exposure. In conclusion, exercise superimposed on heat blunts overall cytokine production and shifts expression to earlier points in time.