Balneotherapy is a clinically effective complementary approach in the treatment of low-grade inflammation- and stress-related pathologies. The biological mechanisms by which immersion in mineral-medicinal water and the application of mud alleviate symptoms of several pathologies are still not completely understood, but it is known that neuroendocrine and immunological responses—including both humoral and cell-mediated immunity—to balneotherapy are involved in these mechanisms of effectiveness; leading to anti-inflammatory, analgesic, antioxidant, chondroprotective, and anabolic effects together with neuroendocrine-immune regulation in different conditions. Hormesis can play a critical role in all these biological effects and mechanisms of effectiveness. The hormetic effects of balneotherapy can be related to non-specific factors such as heat—which induces the heat shock response, and therefore the synthesis and release of heat shock proteins—and also to specific biochemical components such as hydrogen sulfide (H2S) in sulfurous water and radon in radioactive water. Results from several investigations suggest that the beneficial effects of balneotherapy and hydrotherapy are consistent with the concept of hormesis, and thus support a role for hormesis in hydrothermal treatments.

The purpose of the present investigation was to evaluate whether an anti-inflammatory effect together with an improvement of the regulation of the interaction between the inflammatory and stress responses underlies the clinical benefits of pelotherapy in osteoarthritis (OA) patients. This study evaluated the effects of a 10-day cycle of pelotherapy at the spa centre 'El Raposo' (Spain) in a group of 21 OA patients diagnosed with primary knee OA. Clinical assessments included pain intensity using a visual analog scale; pain, stiffness and physical function using the Western Ontario and McMaster Universities Arthritis Index; and health-related quality of life using the EuroQol-5D questionnaire. Serum inflammatory cytokine levels (IL-1β, TNF-α, IL-8, IL-6, IL-10 and TGF-β) were evaluated using the Bio-Plex® Luminex® system. Circulating neuroendocrine-stress biomarkers, such as cortisol and extracellular 72 kDa heat shock protein (eHsp72), were measured by ELISA. After the cycle of mud therapy, OA patients improved the knee flexion angle and OA-related pain, stiffness and physical function, and they reported a better health-related quality of life. Serum concentrations of IL-1β, TNF-α, IL-8, IL-6 and TGF-β, as well as eHsp72, were markedly decreased. Besides, systemic levels of cortisol increased significantly. These results confirm that the clinical benefits of mud therapy may well be mediated, at least in part, by its systemic anti-inflammatory effects and neuroendocrine-immune regulation in OA patients. Thus, mud therapy could be an effective alternative treatment in the management of OA.

Objectives: Balneotherapy with mud application (mud therapy) is a common hydrothermal intervention for the treatment and rehabilitation of elderly patients with osteoarthritis, leading to anti-inflammatory effects. The main purpose of this investigation was to study a role for regulatory T cells in these anti-inflammatory effects. The second objective was to assess whether the neutrophil-mediated innate response is affected by these anti-inflammatory effects. Methods: Thirty-six elderly patients with knee osteoarthritis underwent a 10-day cycle of balneotherapy at a spa center. They received daily sessions of whole-body mud therapy at 40-42 C, using mineral-medicinal water and mud. IL-8 and TGF-b serum concentrations, percentage of circulating CD4 þ CD25 þ FOXP3 þ and CD8 þ CD28regulatory T cells, and neutrophil phagocytic capacity were evaluated at baseline and at the end of the intervention. Clinical assessments included knee flexion and extension angle, pain, stiffness, physical function and health-related quality of life. Results: All clinical outcomes significantly improved. Circulating concentrations of IL-8 and TGF-b decreased, which correlated with decreased pain and improved knee flexion, respectively. Percentage of CD4 þ regulatory T cells decreased, whereas CD8 þ regulatory T cells increased. Neutrophil functional capacity increased. Conclusions: Balneotherapy with mud application was effective in the management of osteoarthritis symptoms. The anti-inflammatory effect mediated by cytokines contributed to the improvement in pain and joint function; and changes in the circulating percentage of regulatory T cells seem to be involved in the anti-inflammatory effects. Improvement in neutrophil function after mud therapy reflects an optimal bioregulatory effect on the inflammatory and innate responses.

An immune-neuroendocrine dysregulation affecting both systemic inflammatory and stress mediators and the function of innate immune cells underlies OA. This reflects an altered feedback between the innate/inflammatory and stress responses in this pathology.

Mud pack therapy is considered an alternative and effective therapy in the clinical management of knee OA. Studies with better methodology are needed to prove its scope.