{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T01:23:32Z","timestamp":1787016212388,"version":"build-2736575974"},"reference-count":41,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2020,5,19]],"date-time":"2020-05-19T00:00:00Z","timestamp":1589846400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["physoc.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Experimental Physiology"],"published-print":{"date-parts":[[2021,1]]},"abstract":"\n New Findings<\/jats:title>\n \n \n \n \n What is the central question of this study?<\/jats:bold>\n <\/jats:p>\n We hypothesized that prior illness would increase the susceptibility to and severity of heat \nstroke (HS).<\/jats:p>\n <\/jats:list-item>\n \n \n What is the main finding and its importance?<\/jats:bold>\n <\/jats:p>\n We provide the first experimental evidence, using a mouse model of HS, that recent viral illness increases the severity of HS. Our data indicate that this effect is not attributable to the exacerbation of hyperthermia but is a consequence of ongoing coagulation and systemic inflammatory reactions. Our data suggest that measurement of platelets, cytokines and chemokines before heat exposure might be indicative of susceptibility to HS, with coagulation and inflammation being potential targets for intervention that could improve recovery.<\/jats:p>\n <\/jats:list-item>\n <\/jats:list>\n <\/jats:p>\n <\/jats:sec>\n \n Abstract<\/jats:title>\n \n It is hypothesized that prior illness exacerbates heat stroke (HS) in otherwise healthy organisms by augmenting hyperthermia during heat exposure or deactivating cellular pathways that protect against organ injury. To test these hypotheses, we injected telemetered male C57BL\/6J mice with lipopolysaccharide (LPS; 50\u00a0\u00b5g\u00a0kg\n \u22121<\/jats:sup>\n i.p<\/jats:sc>\n .) or polyinosinic:polycytidylic acid (PIC; 100\u00a0\u00b5g\n i.p<\/jats:sc>\n .) as a bacterial or a viral mimic, respectively, with saline (SAL; equivalent volume) as a control. Mice recovered for 48 or 72\u00a0h before HS (maximal core temperature\u00a0=\u00a042.4\u00b0C). Platelet counts, cytokines, chemokines and organ injury were determined 48 or 72\u00a0h after injection (without heating) or at maximal core temperature and at 1\u00a0day of recovery from HS. In the absence of heat, PIC induced more robust signs of sickness and increased cytokines and chemokines (TNF\u2010\u03b1, RANTES, IP\u201010 and MIP\u20101\u03b2) at 48\u00a0h, which was not observed with LPS (\n P<\/jats:italic>\n \u00a0<\u00a00.05). Responses of both groups recovered by 72\u00a0h, although low platelet counts persisted after PIC (\n P<\/jats:italic>\n \u00a0<\u00a00.05). Heat\u2010induced hyperthermia was similar among mice injected with SAL, LPS and PIC; however, PIC\u2010injected mice displayed more severe responses during recovery from HS, with reduced survival (48\u00a0h, 70\n versus<\/jats:italic>\n 100%;\n P<\/jats:italic>\n \u00a0<\u00a00.05), deeper and longer post\u2010HS hypothermia, greater reductions in platelets, elevated RANTES, IP\u201010, IL\u20106 and TNF\u2010\u03b1 and greater duodenal injury (\n P<\/jats:italic>\n \u00a0<\u00a00.05). By 72\u00a0h, survival from HS was no longer reduced in PIC\u2010injected mice, although hypothermia, the reduction in platelets and elevated cytokines persisted. Our data indicate that prior illness exacerbates the severity of HS in the absence of signs of illness at the time of heat exposure and suggest that this is attributable to persistent coagulation and inflammatory reactions that might be targets for intervention to improve recovery.\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1113\/ep088480","type":"journal-article","created":{"date-parts":[[2020,5,3]],"date-time":"2020-05-03T00:28:15Z","timestamp":1588465695000},"page":"244-257","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Prior viral illness increases heat stroke severity in mice"],"prefix":"10.1113","volume":"106","author":[{"given":"Shauna M.","family":"Dineen","sequence":"first","affiliation":[{"name":"US Army Research Institute of Environmental Medicine, Thermal Mountain Medicine Division Natick MA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jermaine A.","family":"Ward","sequence":"additional","affiliation":[{"name":"US Army Research Institute of Environmental Medicine, Thermal Mountain Medicine Division Natick MA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2304-8651","authenticated-orcid":false,"given":"Lisa R.","family":"Leon","sequence":"additional","affiliation":[{"name":"US Army Research Institute of Environmental Medicine, Thermal Mountain Medicine Division Natick MA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2020,5,19]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1097\/00024382-199411000-00004"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1378\/chest.104.5.1498"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMra011089"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1097\/01.shk.0000180620.44435.9c"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1123\/jsr.16.3.238"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.3109\/00313028109086837"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2015-11-680744"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1111\/jth.12842"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1038\/cti.2016.39"},{"key":"e_1_2_8_11_1","volume-title":"Textbook of Military Medicine","author":"Gardner J. 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