Acute Phase Response to Exertional Heat Stroke in Mice

Exertional heat stroke (EHS) is a serious illness and a common occurrence for military personnel, athletes, and occupational workers. Innate immunity is vital for cell survival and tissue repair needed for recovery following EHS. Previously, our group revealed a unique cytokine response to EHS where circulating interleukin‐6 (IL‐6) peaked at 0.5 h post EHS; however, little is known about the acute phase response, a subsequent response to IL‐6 signaling. Therefore, we hypothesized that EHS would induce an acute phase response that would be observed in skeletal muscles, hepatocytes, and in the circulation.PurposeTo determine if acute phase proteins (APPs), fibrinogen, lipocalin, and serum amyloid A1 (SAA1) are expressed in liver and skeletal muscle following EHS and whether these result in their accumulation in the circulation.MethodsMice were subject to a standardized EHS protocol using a forced running wheel. While running, the mice experienced environmental temps of 37.5 (EHS) or 22.5 (exercise control) until they experienced loss of consciousness (at a core temperature of ~42.2). The tibialis anterior, soleus, liver, and plasma were collected from the mice (n = 8/group) at 0.5, 3, 24, 96, 216, or 336 h post‐EHS. Tissue samples from exercise controls were retrieved at 3 and 96 h post exercise.ResultsUsing protein immunoblots, a significant increase of SAA1 was observed in liver at 3 h of recovery and peaked at 24 h when compared to the exercise control (2.4 ± 1.2*, 2.5 ± 1.4* vs. 0.1 ± 0.1 AU/total protein; respectively). Moreover, circulating SAA1 was observed at the 3 h time point (5.0 ± 3.8 AU/TP). No difference for SAA1 was observed for any other time points when compared to the control. In the liver, fibrinogen, and lipocalin were undetectable for any of the recovery timepoints. No acute phase proteins were detected in skeletal muscle; although, preliminary data revealed that SAA1 expression is elevated in skeletal muscle during sepsis.ConclusionA single episode of EHS alters the expression of SAA1 in mouse liver and plasma. This observation is consistent with an acute phase response to thermal damage, in response to IL‐6 signaling, initiating cell survival and tissue repair pathways needed for recovery.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.