Immunoinflammatory Regulation Effects of Korean Hot Spring Water

Background: The beneficial clinical effects of Korean hot spring spa therapy, as well as their underlying mechanisms are still poorly understood. We performed a series of clinical and laboratory investigations for better understanding of the clinical effects as well as possible mechanisms of their beneficial effects. Methods: HaCaT cells were prepared and treated with TLR agonist in the presence or absence of HS water for quantification of IL-6, IL-8, GM-CSF, and TNF-α levels. The serum levels of IFN-ɤ, IL-4, IL-5, and IgE were measured. CD4+ naïve cells were allowed to polarize into Th1, Th2, Th17, and Treg cells, and CD4+ and CFSE+ cells were measured for the degree of proliferation. Total RNA from the lesional skin was transcribed into cDNA using a reverse transcription system, and RT-PCR was performed subsequently. Confocal microscopy and RT-PCR were utilized to evaluate the target skin localization of Th cell subsets and associated inflammatory cytokine milieu. Results: Treatment with agonists of TLR 1 through 6 induced attenuation of cytokine production in the exposure to HS water. HS water suppressed the proliferation of Th1, Th2, and Th17 cells with anti-CD3 stimulation, while proliferation and differentiation to Treg cells were promoted under HS water treatment. On RT-PCR of the lesional skin, thymic stromal lymphopoietin (TSLP) mRNA decreased dramatically after bathing with HS. IL-33 mRNA decreased markedly in HS water group as compared to control group. Foxp3 mRNA expression, same as in confocal microscopic finding, showed tendency to increase more in HS. Conclusions: HS water suppressed the proliferation of Th1, Th2, and Th17 cells. In contrast, proliferation and differentiation to Treg cells were promoted under HS water treatment. These results indicate that HS water may affect the distribution of the helper T cells in the immune response, by suppressing the polarization of the Th1, Th2, and Th17 cells. Also, APC induced TNF-α and IL-6 levels were reduced in the presence of HS water. These results showed that TLR-triggered inflammatory responses in APCs might also be modulated under HS water treatment. Overall, our findings suggest that HS spa therapy could be an effective and safe modality for the management of adult AD.