Immunoinflammatory Regulation Effects of Korean Hot Spring Water / 日本温泉気候物理医学会雑誌

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.

Immunoinflammatory Regulation Effects of Korean Hot Spring Water / 日本温泉気候物理医学会雑誌

<b>Background: </b>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.<BR><b>Methods:</b> 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-<i>α</i> 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.<BR><b>Results: </b>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.<BR><b>Conclusions:</b> 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-<i>α</i> 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.

PT2-3 Immunoinflammatory regulation effects of Korean hot spring water / 日本温泉気候物理医学会雑誌

  Spa therapy has long been utilized as one of safe, effective and long-term alternative therapies of various dermatologic diseases in Korea. Among them are pruritic, xerotic, immunoinflammatory, infectious, ulcerative skin diseases. There are about 400 spas in South Korea and many of them are recognized as having specific therapeutic effects. But, the beneficial clinical effects of spa therapy as well as their underlying mechanisms are still poorly defined and understood. In Korea, the area of distribution of hot springs coincide with areas of granite and are distant from geothermal heat energy related to volcanos. Natural hot spring water in South Korea can be classified into four main hydrochemical groups, i.e., Ca(Na)-HCO3, Na(Ca)-HCO3, Na(Ca)-Cl, and acidic Ca-HCO3 type. They are mostly alkaline in nature and have low chemical constituents. We performed a series of clinical and laboratory studies to have better understanding of the clinical effects as well as possible mechanisms of their beneficial effects of several hot springs having different locations and mineral concentrations. They are Haeundae(Na-Cl type), Seokmo-do(Na-Cl, Ca-Cl type), Suanbo(Na-HCO3 type), Baekam(Na-HCO3 type), and Dukku(Na-Cl type) areas. Utilizing human, mice models, and keratinocyte cell lines, we evaluated the effects of each hot spring water on the changes of clinical symptoms of induced dermatitis and their skin barrier functions, skin infiltrating cells and related histologic findings, proinflammatory cytokine production, helper T cell subset differentiation and proliferation. We found that studied hot spring waters, in general, have the capacity to improve skin inflammation of atopic dermatitis and tendencies to downregulate the production of skin inflammatory cytokines and to increase the Foxp3+ Treg cell population while to decrease the Th1, Th2, and Th17 populations.

PT2-3Immunoinflammatory regulation effects of Korean hot spring water / 日本温泉気候物理医学会雑誌

  Spa therapy has long been utilized as one of safe, effective and long-term alternative therapies of various dermatologic diseases in Korea. Among them are pruritic, xerotic, immunoinflammatory, infectious, ulcerative skin diseases. There are about 400 spas in South Korea and many of them are recognized as having specific therapeutic effects. But, the beneficial clinical effects of spa therapy as well as their underlying mechanisms are still poorly defined and understood. In Korea, the area of distribution of hot springs coincide with areas of granite and are distant from geothermal heat energy related to volcanos. Natural hot spring water in South Korea can be classified into four main hydrochemical groups, i.e., Ca(Na)-HCO₃, Na(Ca)-HCO₃, Na(Ca)-Cl, and acidic Ca-HCO₃ type. They are mostly alkaline in nature and have low chemical constituents. We performed a series of clinical and laboratory studies to have better understanding of the clinical effects as well as possible mechanisms of their beneficial effects of several hot springs having different locations and mineral concentrations. They are Haeundae(Na-Cl type), Seokmo-do(Na-Cl, Ca-Cl type), Suanbo(Na-HCO₃ type), Baekam(Na-HCO₃ type), and Dukku(Na-Cl type) areas. Utilizing human, mice models, and keratinocyte cell lines, we evaluated the effects of each hot spring water on the changes of clinical symptoms of induced dermatitis and their skin barrier functions, skin infiltrating cells and related histologic findings, proinflammatory cytokine production, helper T cell subset differentiation and proliferation. We found that studied hot spring waters, in general, have the capacity to improve skin inflammation of atopic dermatitis and tendencies to downregulate the production of skin inflammatory cytokines and to increase the Foxp3⁺ Treg cell population while to decrease the Th1, Th2, and Th17 populations.