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Response of mice to continuous 5-day passive hyperthermia resembles human heat acclimation

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Cell Stress and Chaperones Aims and scope

Abstract

Chronic repeated exposure to hyperthermia in humans results in heat acclimation (HA), an adaptive process that is attained in humans by repeated exposure to hyperthermia and is characterized by improved heat elimination and increased exercise capacity, and acquired thermal tolerance (ATT), a cellular response characterized by increased baseline heat shock protein (HSP) expression and blunting of the acute increase in HSP expression stimulated by re-exposure to thermal stress. Epidemiologic studies in military personnel operating in hot environments and elite athletes suggest that repeated exposure to hyperthermia may also exert long-term health effects. Animal models demonstrate that coincident exposure to mild hyperthermia or prior exposure to severe hyperthermia can profoundly affect the course of experimental infection and injury, but these models do not represent HA. In this study, we demonstrate that CD-1 mice continuously exposed to mild hyperthermia (ambient temperature ~37°C causing ~2°C increase in core temperature) for 5 days and then exposed to a thermal stress (42°C ambient temperature for 40 min) exhibited some of the salient features of human HA, including (1) slower warming during thermal stress and more rapid cooling during recovery and (2) increased activity during thermal stress, as well as some of the features of ATT, including (1) increased baseline expression of HSP72 and HSP90 in lung, heart, spleen, liver, and brain; and (2) blunted incremental increase in HSP72 expression following acute thermal stress. This study suggests that continuous 5-day exposure of CD-1 mice to mild hyperthermia induces a state that resembles the physiologic and cellular responses of human HA. This model may be useful for analyzing the molecular mechanisms of HA and its consequences on host responsiveness to subsequent stresses.

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Grants

Supported by NIH grants GM069431 (ISS) and GM066855, HL69057 and HL085256 (JDH), and by VA Merit Review grants to JDH and ISS.

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No conflicts of interest, financial or otherwise, are declared by the authors.

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Authors and Affiliations

  1. Division of Pulmonary and Critical Care, Department of Medicine, Baltimore VA Medical Center, Baltimore, MD, 21201, USA

    Houtan Sareh, Mohan E. Tulapurkar, Nirav G. Shah, Ishwar S. Singh & Jeffrey D. Hasday

  2. Mucosal Biology Research Center, Baltimore VA Medical Center, Baltimore, MD, 21201, USA

    Nirav G. Shah, Ishwar S. Singh & Jeffrey D. Hasday

  3. Research Services, Baltimore VA Medical Center, Baltimore, MD, 21201, USA

    Ishwar S. Singh & Jeffrey D. Hasday

  4. University of Maryland School of Medicine, Health Science Facility-II, Rm. S347, 20 Penn St, Baltimore, MD, 21201, USA

    Jeffrey D. Hasday

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  1. Houtan Sareh
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  2. Mohan E. Tulapurkar
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  3. Nirav G. Shah
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  4. Ishwar S. Singh
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  5. Jeffrey D. Hasday
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Correspondence to Jeffrey D. Hasday.

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Sareh, H., Tulapurkar, M.E., Shah, N.G. et al. Response of mice to continuous 5-day passive hyperthermia resembles human heat acclimation. Cell Stress and Chaperones 16, 297–307 (2011). https://doi.org/10.1007/s12192-010-0240-8

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