Heat stroke induces a local inflammatory response in skeletal muscle of mice during 24 hours of recovery

Abstract

The systemic inflammatory response to heat stroke (HS) has been well‐characterized, but the effect of passive heat exposure on local inflammation in skeletal muscle is unknown. We hypothesized that passive HS would induce an inflammatory response in skeletal muscle independent of histological damage. The time course of heat shock proteins (HSP‐27, ‐70), toll‐like receptors (TLR‐2, ‐4), myokines (IL‐6, IL‐10, TNF), and a transcription factor (c‐Jun) were measured in the diaphragm of passive HS C57BL/6 mice at maximum core temperature (Tcmax, 42.7ºC), ~3h and 24h of recovery. Histopathology did not show damage to the diaphragm through 24h of recovery. HSP27 decreased at Tcmax, but remained similar to controls from 3–24h of recovery. Conversely, HSP70 increased 40.8% above controls at 24h. TLR2 was not affected by HS but TLR4 showed a 60.3% decrease at Tcmax that returned to baseline by 3h. Remarkable changes were observed in c‐Jun and IL‐10, which increased 55.8% and 73.1% from Tcmax through 3h, respectively. IL‐6 and TNF were similar to controls through 24h. Our results demonstrate a local inflammatory response in skeletal muscle during HS recovery in the absence of tissue damage. IL‐10 may provide protection through HSP stimulation, IL‐6 and TNF inhibition, and induction of cell survival signaling pathways. Research supported by MRMC. Author views not official US Army or DOD policy.