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      Aquatic Exercise at Thermoneutral Water Temperature Enhances Antitumor Immune Responses

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          Abstract

          Despite the broad rehabilitative potential of aquatic exercises, the relationship between aquatic exercise and the immune system has not been fully elucidated to date. In particular, there are few specific and delicate immunological approaches to the effect of water temperature on immunity. Thus, we examined the effect of water temperature on immunity during aquatic exercise. The animal tumor model was adopted to examine the impact of aquatic exercise at thermoneutral temperature (TT; 29°C) on immunity compared with aquatic exercise at body temperature (BT; 36°C). Tumor-bearing mice were made to swim in TT water or in BT water for 3 wk and immune cells and their functional activity were analyzed using FACS. Tumor growth was significantly suppressed in mice that exercised in TT than in BT water. The tumor control correlated with the increased number of NK (2-fold), γδT cells (2.5-fold), NKT (2.5-fold), and cytotoxic CD8 + T cells (1.6-fold), which play a critical role in anti-tumor immune responses. Furthermore, the functional activity was dramatically improved in the TT group, showing enhanced production of IFNγ in CD8 + T cells compared with the BT group. This study demonstrates that aquatic exercise in TT water may improve protective immune responses more effectively than in BT water. Although the effects of water temperature on immune function need further verification in humans, this study suggests that water temperature in human hydrotherapy may be important for improving immune function.

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          How stress influences the immune response.

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            Baseline tumor growth and immune control in laboratory mice are significantly influenced by subthermoneutral housing temperature.

            We show here that fundamental aspects of antitumor immunity in mice are significantly influenced by ambient housing temperature. Standard housing temperature for laboratory mice in research facilities is mandated to be between 20-26 °C; however, these subthermoneutral temperatures cause mild chronic cold stress, activating thermogenesis to maintain normal body temperature. When stress is alleviated by housing at thermoneutral ambient temperature (30-31 °C), we observe a striking reduction in tumor formation, growth rate and metastasis. This improved control of tumor growth is dependent upon the adaptive immune system. We observe significantly increased numbers of antigen-specific CD8(+) T lymphocytes and CD8(+) T cells with an activated phenotype in the tumor microenvironment at thermoneutrality. At the same time there is a significant reduction in numbers of immunosuppressive MDSCs and regulatory T lymphocytes. Notably, in temperature preference studies, tumor-bearing mice select a higher ambient temperature than non-tumor-bearing mice, suggesting that tumor-bearing mice experience a greater degree of cold-stress. Overall, our data raise the hypothesis that suppression of antitumor immunity is an outcome of cold stress-induced thermogenesis. Therefore, the common approach of studying immunity against tumors in mice housed only at standard room temperature may be limiting our understanding of the full potential of the antitumor immune response.
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              Aquatic therapy: scientific foundations and clinical rehabilitation applications.

              The aquatic environment has broad rehabilitative potential, extending from the treatment of acute injuries through health maintenance in the face of chronic diseases, yet it remains an underused modality. There is an extensive research base supporting aquatic therapy, both within the basic science literature and clinical literature. This article describes the many physiologic changes that occur during immersion as applied to a range of common rehabilitative issues and problems. Because of its wide margin of therapeutic safety and clinical adaptability, aquatic therapy is a very useful tool in the rehabilitative toolbox. Through a better understanding of the applied physiology, the practitioner may structure appropriate therapeutic programs for a diverse patient population.
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                Author and article information

                Journal
                Immune Netw
                Immune Netw
                IN
                Immune Network
                The Korean Association of Immunologists
                1598-2629
                2092-6685
                April 2019
                25 February 2019
                : 19
                : 2
                : e10
                Affiliations
                [1 ]Department of Anatomy and Cell Biology, Pusan National University School of Medicine, Yangsan 50612, Korea.
                [2 ]Department of Rehabilitation Medicine, Pusan National University School of Medicine and Research Institute for Convergence of Biomedical Science and Technology, Pusan National University Yangsan Hospital, Yangsan 50612, Korea.
                Author notes
                Correspondence to Changwan Hong. Department of Anatomy and Cell Biology, Pusan National University School of Medicine, Room 504, 49 Busandaehak-ro, Yangsan 50612, Korea. chong@ 123456pusan.ac.kr
                Author information
                https://orcid.org/0000-0001-7894-0930
                https://orcid.org/0000-0003-2567-2973
                Article
                2019190203
                10.4110/in.2019.19.e10
                6494765
                cb38b481-63b6-4da0-abfe-cc2313dd104b
                Copyright © 2019. The Korean Association of Immunologists

                This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License ( https://creativecommons.org/licenses/by-nc/4.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 20 November 2018
                : 21 December 2018
                : 27 December 2018
                Funding
                Funded by: Pusan National University, CrossRef https://doi.org/10.13039/501100002543;
                Categories
                Original Article

                Immunology
                aquatic exercise,t cells,interferons,tumor model,thermoneutral
                Immunology
                aquatic exercise, t cells, interferons, tumor model, thermoneutral

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