Aquatic Exercise at Thermoneutral Water Temperature Enhances Antitumor Immune Responses

다국어 초록 (Multilingual 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.

참고문헌 (Reference)

1 Karp CL, "Unstressing intemperate models: how cold stress undermines mouse modeling" 209 : 1069-1074, 2012

2 Won SJ, "Thermal stresses reduce natural killer cell cytotoxicity" 79 : 732-737, 1995

3 Fridman WH, "The immune contexture in human tumours: impact on clinical outcome" 12 : 298-306, 2012

4 Batterham SI, "Systematic review and meta-analysis comparing land and aquatic exercise for people with hip or knee arthritis on function, mobility and other health outcomes" 12 : 123-, 2011

5 Aarstad HJ, "Stress causes reduced natural killer activity in mice" 18 : 461-464, 1983

6 Lee YJ, "Steady-state production of IL-4 modulates immunity in mouse strains and is determined by lineage diversity of iNKT cells" 14 : 1146-1154, 2013

7 Kim G, "Soluble γc receptor attenuates anti-tumor responses of CD8+ T cells in T cell immunotherapy" 143 : 1212-1223, 2018

8 Lee B, "Soluble common gamma chain exacerbates COPD progress through the regulation of inflammatory T cell response in mice" 12 : 817-827, 2017

9 Hong C, "Regulation of secondary antigen-specific CD8+ T-cell responses by natural killer T cells" 69 : 4301-4308, 2009

10 Shu J, "Modulation of cellular immune responses by cold water swim stress in the rat" 17 : 357-371, 1993

11 Holloszy JO, "Longevity of cold-exposed rats: a reevaluation of the “rate-of-living theory" 61 : 1656-1660, 1986

12 Davis MS, "Influx of neutrophils and persistence of cytokine expression in airways of horses after performing exercise while breathing cold air" 68 : 185-189, 2007

13 Cheng GJ, "Immunosuppression in mice induced by cold water stress" 4 : 278-291, 1990

14 Janský L, "Immune system of cold-exposed and cold-adapted humans" 72 : 445-450, 1996

15 Brenner IK, "Immune changes in humans during cold exposure: effects of prior heating and exercise" 87 : 699-710, 1999

16 Gober HJ, "Human T cell receptor γδ cells recognize endogenous mevalonate metabolites in tumor cells" 197 : 163-168, 2003

17 Padgett DA, "How stress influences the immune response" 24 : 444-448, 2003

18 Rolot M, "Helminth-induced IL-4 expands bystander memory CD8+ T cells for early control of viral infection" 9 : 4516-, 2018

19 Shimizu I, "Enhanced thermal avoidance in mice lacking the ATP receptor P2X3" 116 : 96-108, 2005

20 Aviles H, "Effects of cold stress on spleen cell proliferation and cytokine production during chronic Toxoplasma gondii infection" 11 : 93-102, 2004

21 Pöyhönen T, "Effects of aquatic resistance training on neuromuscular performance in healthy women" 34 : 2103-2109, 2002

22 박희정, "Effect of IL-4 on the Development and Function of Memory-like CD8 T Cells in the Peripheral Lymphoid Tissues" 대한면역학회 16 (16): 126-133, 2016

23 Banerjee SK, "Cold stress-induced modulation of cell immunity during acute Toxoplasma gondii infection in mice" 85 : 442-447, 1999

24 Shephard RJ, "Cold exposure and immune function" 76 : 828-836, 1998

25 Goundasheva D, "Changes in some parameters of the immune response in rats after cold stress" 41 : 670-674, 1994

26 Sundaresan G, "Certain immunological parameters in subacute cold stress" 34 : 57-60, 1990

27 Hong C, "CD4+ T cells in the absence of the CD8+ cytotoxic T cells are critical and sufficient for NKT cell-dependent tumor rejection" 177 : 6747-6757, 2006

28 Cannon B, "Brown adipose tissue: function and physiological significance" 84 : 277-359, 2004

29 Terrien J, "Behavioral thermoregulation in mammals: a review" 16 : 1428-1444, 2011

30 Kokolus KM, "Baseline tumor growth and immune control in laboratory mice are significantly influenced by subthermoneutral housing temperature" 110 : 20176-20181, 2013

31 Becker BE, "Aquatic therapy: scientific foundations and clinical rehabilitation applications" 1 : 859-872, 2009

32 Yang Q, "Antitumor activity of NK cells" 36 : 13-25, 2006

33 Nguyen KD, "Alternatively activated macrophages produce catecholamines to sustain adaptive thermogenesis" 480 : 104-108, 2011