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Thirty participants who met DSM-IV-TR criteria for MDD were randomized to receive a single session of WBH (<jats:italic>n<\/jats:italic>\u2009=\u200916) or sham treatment (<jats:italic>n<\/jats:italic>\u2009=\u200914). Hamilton Depression Rating Scale (HDRS) scores were assessed at baseline and 1, 2, 4, and 6 weeks post-treatment (WBH vs. sham), and plasma cytokine concentrations were assessed at baseline, immediately post-treatment, and 1 and 4 weeks post-treatment. As previously reported, WBH produced a rapid and sustained antidepressant effect. When compared to sham, WBH increased plasma interleukin (IL)-6 immediately post-treatment (time by treatment: <jats:italic>\u03c7<\/jats:italic><jats:sup>2<\/jats:sup><jats:sub>(3, <jats:italic>N<\/jats:italic>=108)<\/jats:sub>\u2009=\u200947.33, <jats:italic>p<\/jats:italic>\u2009&lt;\u20090.001), while having no effect on other cytokines acutely and no impact on IL-6, or any other cytokine, at 1 or 4 weeks post treatment. In the study sample as a whole, increased IL-6 post-treatment was associated with reduced HDRS depression scores over the 6 weeks of follow-up (<jats:italic>F<\/jats:italic><jats:sub>(1, 102.3)<\/jats:sub>\u2009=\u20096.74, <jats:italic>p<\/jats:italic>\u2009=\u20090.01). These results suggest a hitherto unrecognized relationship between hyperthermia, the immune system, and depression, and may point to WBH as a novel modality for exploring behavioral effects of IL-6 when the cytokine is activated in isolation from the inflammatory mediators with which it frequently travels.<\/jats:p>","DOI":"10.1038\/s41398-023-02402-9","type":"journal-article","created":{"date-parts":[[2023,4,21]],"date-time":"2023-04-21T09:09:51Z","timestamp":1682068191000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Association of plasma cytokines and antidepressant response following mild-intensity whole-body hyperthermia in major depressive disorder"],"prefix":"10.1038","volume":"13","author":[{"given":"Michael C.","family":"Flux","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7858-3785","authenticated-orcid":false,"given":"David G.","family":"Smith","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John J. 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DGS reports no financial relationships with commercial interests. JJB reports no financial relationships with commercial interests. MRM reports no financial relationships with commercial interests. AM reports no financial relationships with commercial interests. TKB reports no financial relationships with commercial interests. BHM reports no financial relationships with commercial interests. BMM serves as an employee and shareholder of Mycobacterium Therapeutics Corporation. SPC reports no financial relationships with commercial interests. CAL serves on the Scientific Advisory Board of Immodulon Therapeutics, Ltd., is Cofounder and Chief Scientific Officer of Mycobacteria Therapeutics Corporation, serves as an unpaid scientific consultant to Aurum Switzerland AG, and is a member of the faculty of the Integrative Psychiatry Institute, Boulder, Colorado. CLR serves as a consultant to Usona Institute, Novartis, Biogen\/Sage, and Emory Healthcare.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"132"}}