The antidepressant effect of whole-body hyperthermia is associated with the classical interleukin-6 signaling pathway.
Level 2 - randomized trial
Secondary analysis of an individual randomized controlled trial
PubMed 38677624 · doi:10.1016/j.bbi.2024.04.040
What was done
A secondary data analysis of a 6-week, randomized, double-blind, sham-controlled trial comparing whole-body hyperthermia to a sham procedure in medication-free adults (aged 18–65) with major depressive disorder and baseline Hamilton Depression Rating Scale (17-item) score ≥ 16. Of 338 screened individuals, 34 were randomized, 30 received interventions, and 26 completed ≥ 2 blood draws and depressive symptom assessments (n = 12 active hyperthermia, n = 14 sham). The ratio of interleukin-6 (IL-6) to soluble IL-6 receptor (sIL-6R) was measured pre-intervention, post-intervention, and at weeks 1 and 4. Hierarchical linear modeling evaluated whether post-intervention ratio changes moderated depressive symptoms across weeks 1, 2, 4, and 6.
What was found
Active whole-body hyperthermia significantly increased the IL-6:sIL-6R ratio immediately post-treatment compared to sham [F(3,72) = 11.73, p < .001], but differences were not present pre-intervention or at weeks 1 and 4. In hierarchical linear modeling, post-intervention increases in the IL-6:sIL-6R ratio moderated depressive symptoms, associating with significant symptom reductions at weeks 1, 2, 4, and 6 in the active group compared to sham (B = -229.44, t = -3.82, p < .001).
Why it matters
This study provides mechanistic evidence that acute activation of classical IL-6 signaling may mediate the sustained antidepressant efficacy of whole-body hyperthermia.
Limits
The sample size for this secondary analysis was very small (n = 26), and raw biomarker values were not provided in the abstract. Causal direct manipulation of IL-6 signaling was not conducted, and findings may not generalize beyond medication-free patients.
Cited by
- supports The magnitude of acute IL-6 elevation from whole-body hyperthermia strongly correlated with antidepressant response one week later.