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Fever and the thermal regulation of immunity: the immune system feels the heat

Evans et al., Nature Reviews Immunology, doi:10.1038/nri3843
May 2015  
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Review of fever and the thermal regulation of immunity. Authors discuss how the evolutionary conservation of fever for over 600 million years argues for a protective role, with the survival benefit outweighing the metabolic cost. Febrile temperatures are proposed to boost innate and adaptive immunity through several mechanisms. These include improving neutrophil bactericidal activity, natural killer cell cytotoxicity, dendritic cell migration and antigen presentation, and lymphocyte trafficking into lymphoid tissues. Interleukin-6 is highlighted as a key mediator of both fever and lymphocyte homing through an endothelial trans-signalling mechanism involving soluble IL-6 receptor alpha. Thermal signals are also implicated in attenuating inflammation during recovery from infection. Additionally, new data reveals overlapping signaling pathways between fever-induced thermogenesis and immune cell function, suggesting tight interplay between temperature regulation and immunity.
Reviews covering thermotherapy for COVID-19 include Cohen, Evans, Kunutsor, Larenas-Linnemann, Mancilla-Galindo, Ramirez.
Evans et al., 15 May 2015, peer-reviewed, 3 authors.
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Fever and the thermal regulation of immunity: the immune system feels the heat
Sharon S Evans, Elizabeth A Repasky, Daniel T Fisher
Nature Reviews Immunology, doi:10.1038/nri3843
Fever is a cardinal response to infection that has been conserved in warm-blooded and cold-blooded vertebrates for more than 600 million years of evolution. The fever response is executed by integrated physiological and neuronal circuitry and confers a survival benefit during infection. In this Review, we discuss our current understanding of how the inflammatory cues delivered by the thermal element of fever stimulate innate and adaptive immune responses. We further highlight the unexpected multiplicity of roles of the pyrogenic cytokine interleukin-6 (IL-6), both during fever induction and during the mobilization of lymphocytes to the lymphoid organs that are the staging ground for immune defence. We also discuss the emerging evidence suggesting that the adrenergic signalling pathways associated with thermogenesis shape immune cell function.
Competing interests statement The authors declare no competing interests.
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