Association of plasma cytokines and antidepressant response following mild-intensity whole-body hyperthermia in major depressive disorder

Michael C. Flux, David G. Smith, John J.B. Allen, Matthias R. Mehl, Andi Medrano, Tommy K. Begay, Brandon H. Middlemist, Brandon M. Marquart, Steven P. Cole, Christina J. Sauder, Christopher A. Lowry, Charles L. Raison

Research output: Contribution to journalArticlepeer-review

4 Scopus citations


Whole-body hyperthermia (WBH) shows promise for the treatment of major depressive disorder (MDD). Because MDD is associated with increased inflammation, and anti-inflammatory agents show some promise as antidepressants, the current study sought to identify the acute and longer-term immune effects of WBH in participants with MDD and to explore whether these effects associate with the procedure’s antidepressant properties. Thirty participants who met DSM-IV-TR criteria for MDD were randomized to receive a single session of WBH (n = 16) or sham treatment (n = 14). 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: χ2(3, N=108) = 47.33, p < 0.001), 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 (F(1, 102.3) = 6.74, p = 0.01). 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.

Original languageEnglish (US)
Article number132
JournalTranslational psychiatry
Issue number1
StatePublished - Dec 2023
Externally publishedYes

ASJC Scopus subject areas

  • Psychiatry and Mental health
  • Cellular and Molecular Neuroscience
  • Biological Psychiatry


Dive into the research topics of 'Association of plasma cytokines and antidepressant response following mild-intensity whole-body hyperthermia in major depressive disorder'. Together they form a unique fingerprint.

Cite this