Dear Editor, In this historical moment (COVID-19 infection spreading worldwide), we think it is interesting to know whether balneotherapy applications as mud-bath therapy or hydrotherapy applications can affect the immune system. Many mineral-rich waters have been shown to have effects on the immune system and recent findings suggest that balneotherapy may improve the efficacy of immune response. The mechanisms through which immersion in mineral-rich water or mud therapy may be useful to improve human immune function are still not completely understood, but surely neuroendocrine and immunological responses, including both innate and adaptive immunity, and also cell-mediated and humoral immunity, are involved. Concerning cell-mediated immunity, balneotherapy applications can improve the survival capacity and activity of neutrophils. Rinaldi et al. (2006) demonstrated in vitro that sulphurous mineral water favours the short-term survival of neutrophils, speeding up the resolution of infections and preventing further inflammation. Studies conducted in patients with osteoarthritis who underwent hydrotherapy or mud-bath therapy showed that, after the treatment, neutrophils’ circulating and functional capacity increased, reflecting a greater defence capacity against pathogens and thus a potential lower susceptibility to infections (Gálvez et al. 2017, 2018a, 2018b). Balneotherapy may also contribute to increase cortisol levels in healthy and subhealthy people. Changes in cortisol levels suggest that mineral baths may modulate the activity of the hypothalamic-pituitary-adrenal axis, inducing a transitorily but significant rise in ACTH production (Antonelli and Donelli 2018). It is possible to hypothesize that an increase in the systemic concentrations of cortisol after balneotherapy could mediate the stimulation of the phagocytic activity of neutrophils in patients with osteoarthritis (Ortega et al. 2017). Also, radon bath therapy can influence cellmediated immunity by giving a small but long-lasting increase in monocytes (Rühle et al. 2017). Regarding the adaptive immunity, immersions in hot baths can increase, probably depending on an increased somatotropic hormone production, the total number and the activity of CD8+ lymphocytes and natural killer cells, important in neutralizing, killing and rejecting cells infected by viruses (Blazícková et al. 2000). On the other hand, Piao et al. (2020) investigated immune function changes in the peripheral blood of people living near radon hot springs, demonstrating an increase in the percentage of CD4+ cells, that induce T and B lymphocytes proliferation, and a reduction in the percentage of CD8+ cells. Balneotherapy can also normalize the proportion of Th1, Th2, Th17 and Treg CD4+ lymphocytes. Th1 cells have a cytotoxic activity against intracellular pathogens (such as viruses,Mycobacterium tuberculosis); Th2 cells regulate humoral immunity and allergic responses, whereas the Th17 family is involved in the defence against extracellular pathogens. Th17 cells are pro-inflammatory lymphocytes, while Treg cells have a suppressor activity. A fine balance between Th17 and Treg CD4+ lymphocytes has emerged as a crucial point in the inflammation associated with autoimmune and immune-mediated diseases. Sulphur balneotherapy seems to have a role in the activation of both polarization pathways (Vitale 2018), while in patients who followed bath applications over 3 weeks with low dose radon, only Treg cells were increased after the treatment and Th17 cells were unchanged (Cucu et al. 2017). Regarding the modulation of inflammatory cytokines’ activity, mud therapy and balneotherapy can cause a reduction in serum concentrations of pro-inflammatory cytokines TNF-α and IL-1β as well as an increase in anti-inflammatory IGF-1 (Gálvez et al. 2018a, 2018b). In a psoriasis-like murinemodel, balneotherapy suppressed lesional IL-23 and IL-17A, cytokines involved in maintaining chronic inflammation (Lee et al. 2014). C-reactive protein levels, which rise in response * Stefano Masiero stef.masiero@unipd.it

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COVID-19时代的浴疗与人体免疫功能

亲爱的编辑，在这个历史性时刻（COVID-19 感染在全球蔓延），我们认为了解浴疗应用如泥浴疗法或水疗应用是否会影响免疫系统很有趣。许多富含矿物质的水已被证明对免疫系统有影响，最近的研究结果表明，浴疗可能会提高免疫反应的功效。浸泡在富含矿物质的水或泥浆疗法中可能有助于改善人体免疫功能的机制仍未完全了解，但肯定是神经内分泌和免疫反应，包括先天性和适应性免疫，以及细胞介导和体液免疫，涉及。关于细胞介导的免疫，浴疗应用可以提高中性粒细胞的存活能力和活性。里纳尔迪等人。(2006) 在体外证明含硫矿泉水有利于中性粒细胞的短期存活，加速感染的解决并防止进一步的炎症。对接受水疗或泥浴疗法的骨关节炎患者进行的研究表明，治疗后中性粒细胞的循环和功能能力增加，反映了对病原体的更强防御能力，从而降低了对感染的潜在可能性（Gálvez et al. 2017 , 2018a, 2018b)。浴疗也可能有助于增加健康和亚健康人群的皮质醇水平。皮质醇水平的变化表明，矿泉浴可能会调节下丘脑 - 垂体 - 肾上腺轴的活动，导致 ACTH 产生暂时但显着增加（Antonelli 和 Donelli 2018）。有可能假设浴疗后全身皮质醇浓度的增加可能介导骨关节炎患者中性粒细胞吞噬活性的刺激（Ortega 等人，2017 年）。此外，氡浴疗法可以通过使单核细胞少量但持久的增加来影响细胞介导的免疫（Rühle 等人，2017 年）。关于适应性免疫，泡热水浴可以增加，这可能取决于生长激素的产生、CD8+ 淋巴细胞和自然杀伤细胞的总数和活性，这对于中和、杀死和排斥被病毒感染的细胞很重要（Blazícková 等人） . 2000）。另一方面，Piao 等人。(2020) 调查氡温泉附近居民外周血免疫功能变化，证明诱导 T 和 B 淋巴细胞增殖的 CD4+ 细胞百分比增加，以及 CD8+ 细胞百分比减少。浴疗还可以使 Th1、Th2、Th17 和 Treg CD4+ 淋巴细胞的比例正常化。Th1细胞对细胞内病原体（如病毒、结核分枝杆菌）具有细胞毒活性；Th2 细胞调节体液免疫和过敏反应，而 Th17 家族参与防御细胞外病原体。Th17 细胞是促炎性淋巴细胞，而 Treg 细胞具有抑制活性。Th17 和 Treg CD4+ 淋巴细胞之间的良好平衡已成为与自身免疫和免疫介导疾病相关的炎症的关键点。硫磺浴疗法似乎在激活两种极化途径中都有作用（Vitale 2018），而在使用低剂量氡浴 3 周以上的患者中，只有 Treg 细胞在治疗后增加，而 Th17 细胞没有变化（Cucu 等2017 年）。关于炎症细胞因子活性的调节，泥疗和浴疗可导致促炎细胞因子 TNF-α 和 IL-1β 的血清浓度降低以及抗炎 IGF-1 的增加（Gálvez et al. 2018a , 2018b)。在银屑病样小鼠模型中，浴疗抑制了病变 IL-23 和 IL-17A，它们是参与维持慢性炎症的细胞因子（Lee 等人，2014 年）。C 反应蛋白水平，响应上升 * Stefano Masiero stef.masiero@unipd.it 而在使用低剂量氡浴 3 周以上的患者中，只有 Treg 细胞在治疗后增加，而 Th17 细胞没有变化（Cucu 等人，2017 年）。关于炎症细胞因子活性的调节，泥疗和浴疗可导致促炎细胞因子 TNF-α 和 IL-1β 的血清浓度降低以及抗炎 IGF-1 的增加（Gálvez et al. 2018a , 2018b)。在银屑病样小鼠模型中，浴疗抑制了病变 IL-23 和 IL-17A，它们是参与维持慢性炎症的细胞因子（Lee 等人，2014 年）。C 反应蛋白水平，响应上升 * Stefano Masiero stef.masiero@unipd.it 而在使用低剂量氡浴 3 周以上的患者中，只有 Treg 细胞在治疗后增加，而 Th17 细胞没有变化（Cucu 等人，2017 年）。关于炎症细胞因子活性的调节，泥疗和浴疗可导致促炎细胞因子 TNF-α 和 IL-1β 的血清浓度降低以及抗炎 IGF-1 的增加（Gálvez et al. 2018a , 2018b)。在银屑病样小鼠模型中，浴疗抑制了病变 IL-23 和 IL-17A，它们是参与维持慢性炎症的细胞因子（Lee 等人，2014 年）。C 反应蛋白水平，响应上升 * Stefano Masiero stef.masiero@unipd.it 关于炎症细胞因子活性的调节，泥疗和浴疗可导致促炎细胞因子 TNF-α 和 IL-1β 的血清浓度降低以及抗炎 IGF-1 的增加（Gálvez et al. 2018a , 2018b)。在银屑病样小鼠模型中，浴疗抑制了病变 IL-23 和 IL-17A，它们是参与维持慢性炎症的细胞因子（Lee 等人，2014 年）。C 反应蛋白水平，响应上升 * Stefano Masiero stef.masiero@unipd.it 关于炎症细胞因子活性的调节，泥疗和浴疗可导致促炎细胞因子 TNF-α 和 IL-1β 的血清浓度降低以及抗炎 IGF-1 的增加（Gálvez et al. 2018a , 2018b)。在银屑病样小鼠模型中，浴疗抑制了病变 IL-23 和 IL-17A，它们是参与维持慢性炎症的细胞因子（Lee 等人，2014 年）。C 反应蛋白水平，响应上升 * Stefano Masiero stef.masiero@unipd.it 参与维持慢性炎症的细胞因子（Lee 等人，2014 年）。C 反应蛋白水平，响应上升 * Stefano Masiero stef.masiero@unipd.it 参与维持慢性炎症的细胞因子（Lee 等人，2014 年）。C 反应蛋白水平，响应上升 * Stefano Masiero stef.masiero@unipd.it