title: Fever, immunity, and molecular adaptations.
abstract: The heat shock response (HSR) is an ancient and highly conserved process that is essential for coping with environmental stresses, including extremes of temperature. Fever is a more recently evolved response, during which organisms temporarily subject themselves to thermal stress in the face of infections. We review the phylogenetically conserved mechanisms that regulate fever and discuss the effects that febrile-range temperatures have on multiple biological processes involved in host defense and cell death and survival, including the HSR and its implications for patients with severe sepsis, trauma, and other acute systemic inflammatory states. Heat shock factor-1, a heat-induced transcriptional enhancer is not only the central regulator of the HSR but also regulates expression of pivotal cytokines and early response genes. Febrile-range temperatures exert additional immunomodulatory effects by activating mitogen-activated protein kinase cascades and accelerating apoptosis in some cell types. This results in accelerated pathogen clearance, but increased collateral tissue injury, thus the net effect of exposure to febrile range temperature depends in part on the site and nature of the pathologic process and the specific treatment provided.
authors.affiliation: Division of Pulmonary and Critical Care Medicine, Department of Medicine, University of Maryland School of Medicine and the Baltimore V.A. Medical Center, Baltimore, Maryland.
authors.forename: Jeffrey D
authors.initials: JD
authors.lastname: Hasday
authors.forename: Christopher
authors.initials: C
authors.lastname: Thompson
authors.forename: Ishwar S
authors.initials: IS
authors.lastname: Singh
mesh_terms: D000818:Animals; D001424:Bacterial Infections / Q000503:physiopathology; D001833:Body Temperature Regulation / Q000502:physiology; D004268:DNA-Binding Proteins / Q000502:physiology; D005334:Fever / Q000276:immunology / Q000382:microbiology / Q000503:physiopathology*; D000076249:Heat Shock Transcription Factors; D018869:Heat-Shock Response / Q000235:genetics / Q000276:immunology / Q000502:physiology*; D006801:Humans; D013312:Stress, Physiological / Q000276:immunology; D014157:Transcription Factors / Q000502:physiology
chemical_list: D004268:DNA-Binding Proteins; D000076249:Heat Shock Transcription Factors; D014157:Transcription Factors