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Neuroimmunomodulation induced by mud-bath therapy: clinical benefits and bioregulation of the innate immune response

cohort Grade B 2025 Open access
Authors: Ortega-Collazos, Eduardo, Otero, Eduardo, Torres-Piles, Silvia, López-Jurado, Casimiro, Navarro, Carmen, Martín-Cordero, Leticia, Gálvez, Isabel, Hinchado, María Dolores, Ortega, Eduardo
Journal: International Journal of Biometeorology 69 : 2115–2124
DOI: 10.1007/s00484-025-02984-7

Key Findings

  • 23 elderly OA patients, 10-day hyperthermic mud-bath with RosA-enriched peloid at 40°C — verified from PDF
  • Significant increase in systemic cortisol levels post-intervention — HPA axis activation — verified
  • Notable decrease in IL-8 inflammatory marker — verified
  • Enhanced phagocytic and microbicidal activity of neutrophils (flow cytometry) — verified
  • Improved knee mobility and reduced pain, reduced analgesic use — verified
  • Proposes immuno-neuroendocrine stabilization as mechanism: cortisol ↑ + IL-8 ↓ + neutrophil function ↑ — verified
  • Hormetic stress response: mud-bath acts as mild physiological stressor triggering adaptive benefit — verified

Clinical study demonstrating that hyperthermic mud-bath therapy induces immuno-neuroendocrine stabilization in elderly OA patients. Key mechanistic finding: the intervention activates the HPA axis (increased cortisol), which suppresses inflammatory mediators (decreased IL-8) while simultaneously enhancing innate immune function (improved neutrophil phagocytic and microbicidal activity).

Verified Findings (from PDF)

  • Cortisol: Significant increase post-intervention — reflects HPA axis activation by hyperthermic stress
  • IL-8: Notable decrease — anti-inflammatory effect mediated through cortisol-driven immunomodulation
  • Neutrophils: Enhanced phagocytic and microbicidal capacity — innate immune stimulation
  • Clinical: Improved knee mobility, reduced pain, reduced analgesic use
  • Framework: Proposes “immunoneuroendocrine stabilization” as unifying mechanism — hormetic stress response normalizes the dysregulated stress-inflammation interaction in OA

Significance for Knowledge Graph

Introduces a new mechanistic concept — neuroimmunomodulation — where the therapeutic benefit comes not from direct anti-inflammatory action but from normalizing the neuro-endocrine regulation of immunity. This is distinct from the direct cytokine inhibition by humic acids (van-rensburg-2015) and suggests a whole-body regulatory effect beyond local tissue actions.

neuroimmunomodulationcortisolIL-8neutrophilsHPA-axishormesisosteoarthritisinnate-immunityclinical