title: Fever, temperature, and the immune response.
abstract: Fever's ability to manipulate the character and extent of physiological temperature gradients correlates with the unusual influence different physiological temperatures have upon model immune responses in vitro. This relationship may help to explain the remarkable evolutionary conservation of the febrile response to infection. A very restricted range of the upper physiological temperatures supports the activation of resting lymphocytes for proliferation and effector formation in the two major limbs of the immune system, cell-mediated immunity and humoral immunity. In contrast, once effectors are formed they can function in a fashion which is nearly independent of physiological temperature. This suggests that physiological temperature change acts to regulate the emergence of new immune responses but does not restrict the activity of existing effector mechanisms once they have been formed. The differential sensitivity of these processes to different physiological temperatures suggests that fever's biological purpose with respect to the immune system is the elimination of lower peripheral tissue temperatures rather than the elevation of core temperatures. However, further studies may reveal that some functions are amplified by the core temperature transitions while other functions are selectively regulated by peripheral tissue temperature transitions. The critical cell for the temperature dependence of immune responses seems to be the Th since its ability to produce cytokines is highly temperature dependent. In contrast, macrophages produce cytokines equally well at all temperatures except those of the febrile core, a feature which may serve to downregulate the production of endogenous pyrogens.
authors.affiliation: Department of Biology, Washington University, St. Louis, Missouri 63130, USA. hanson@biodec.wustl.edu
authors.forename: D F
authors.initials: DF
authors.lastname: Hanson
mesh_terms: D001831:Body Temperature; D002455:Cell Division; D002460:Cell Line; D016207:Cytokines / Q000502:physiology; D003602:Cytotoxicity, Immunologic; D004247:DNA / Q000096:biosynthesis; D005334:Fever / Q000503:physiopathology*; D006801:Humans; D007109:Immunity; D007375:Interleukin-1 / Q000096:biosynthesis; D007376:Interleukin-2 / Q000096:biosynthesis; D008213:Lymphocyte Activation; D008214:Lymphocytes / Q000276:immunology; D008264:Macrophages / Q000276:immunology; D011749:Pyrogens / Q000502:physiology; D013154:Spleen / Q000166:cytology; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology; D013950:Thymus Gland / Q000166:cytology
chemical_list: D016207:Cytokines; D007375:Interleukin-1; D007376:Interleukin-2; D011749:Pyrogens; D004247:DNA