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We tested the hypothesis that skeletal muscle exhibits a cytokine response to HS that parallels the systemic response in conscious mice heated to a core temperature of 42.4\u00b0C (T<jats:sub>cMax<\/jats:sub>). Diaphragm and hindlimb muscles showed a rapid rise in interleukin-6 (IL-6) and interleuin-10 (IL-10) mRNA and transient inhibition of tumor necrosis factor-\u03b1 (TNF-\u03b1) and interleukin-1\u03b2 (IL-1\u03b2) throughout early recovery, a pattern that parallels changes in circulating cytokines. IL-6 protein was transiently elevated in both muscles at \u223c32 min after reaching T<jats:sub>cMax<\/jats:sub>. Other responses observed included an upregulation of toll-like receptor-4 (TLR-4) and heat shock protein-72 (HSP-72) mRNA but no change in TLR-2 or HSP25 mRNA. Furthermore, c-jun and c-fos mRNA increased. Together, c-jun\/c-fos form the activator protein-1 (AP-1) transcription factor, critical for stress-induced regulation of IL-6. Interestingly, a second \u201clate-phase\u201d (24 h) cytokine response, with increases in IL-6, IL-10, IL-1\u03b2, and TNF-\u03b1 protein, were observed in hindlimb but not diaphragm muscle. These results demonstrate that skeletal muscle responds to HS with a distinct \u201cstress-induced immune response,\u201d characterized by an early upregulation of IL-6, IL-10, and TLR-4 and suppression of IL-1\u03b2 and TNF-\u03b1 mRNA, a pattern discrete from classic innate immune cytokine responses. <\/jats:p>","DOI":"10.1152\/japplphysiol.00636.2013","type":"journal-article","created":{"date-parts":[[2013,8,9]],"date-time":"2013-08-09T05:00:43Z","timestamp":1376024443000},"page":"1126-1137","source":"Crossref","is-referenced-by-count":77,"title":["Heat stroke activates a stress-induced cytokine response in skeletal muscle"],"prefix":"10.1152","volume":"115","author":[{"given":"Steven S.","family":"Welc","sequence":"first","affiliation":[{"name":"Thermal and Mountain Medicine Division, U.S. Army Research Institute of Environmental Medicine, Natick, Massachusetts;"},{"name":"Department of Applied Physiology and Kinesiology, College of Health and Human Performance, University of 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