Unveiling the immunomodulatory mechanisms of fever-range whole-body hyperthermia in humans: Insights from miRNA and protein mediators.

Fever-range whole-body hyperthermia (frWBH) is widely used as an adjunctive therapy for various conditions, including rheumatic diseases, psychiatric disorders, and cancer. Despite its extensive application, the biological and immunological mechanisms underlying frWBH remain poorly understood. To investigate the molecular mechanisms driving its therapeutic effects, we conducted a comprehensive analysis encompassing miRNA expression profiling using RT-qPCR, white blood cell (WBC) count assessment, and plasma proteomic profiling immediately following frWBH treatment. Additionally, free cortisol levels were measured using ELISA in post-treatment saliva samples to evaluate the stress response. Our results demonstrate that frWBH induces alterations in leukocyte populations via a cortisol-independent mechanism. Notably, frWBH enhanced the expression of granulocyte colony-stimulating factor (G-CSF), correlating with increased granulocyte counts. Moreover, elevated levels of macrophage inhibitory protein (MIP-1α), miR-130a, and miR-155 in patient serum suggest that frWBH serves as a robust immunomodulatory intervention, primarily stimulating innate immune responses. Collectively, these findings establish frWBH as a potent immunomodulator capable of eliciting distinct molecular and cellular responses, underscoring its therapeutic potential across a wide range of clinical applications.