title: The neurobiology of the human febrile response.
abstract: Fever is a normal adaptation in response to a pyrogenic stimulus resulting in the generation of cytokines and prostaglandins. Fever differs from hyperpyrexia and hyperthermia associated with hot environs and pharmacological triggers. Typically, pyrogens are infectious organisms or their direct products (toxins). The body produces a wide array of pyrogenic cytokines such as interleukins (IL-1, IL-6), interferon, and tumor necrosis factor. Tissue trauma can trigger the febrile response, as can infectious organisms, certain medications, and blood products. The circumventricular organ system (CVOS) is neuronal tissues lying outside the blood-brain barrier that has a key role in initiating the communication sequence responsible for the synthesis of febrile prostaglandins. When pyrogenic cytokines are detected by the CVOS, prostaglandin synthesis, especially cyclooxygenase-dependent prostaglandin E2, is induced, activating the febrile response. Once the appropriate signal is received by the hypothalamus, autonomic, endocrine, and behavioral processes are activated until the hypothalamic set-point is reset downward as a consequence of a reduction in pyrogen content or antipyretic therapy, with subsequent heat loss. There is little evidence that fever facilitates recovery from disease or assists the immune system in mounting a response. Antipyretics are used commonly to decrease the distressing manifestations associated with fever.
authors.affiliation: Virginia Commonwealth University, Richmond, USA. cbiddle@hsc.vcu.edu
authors.forename: Chuck
authors.initials: C
authors.lastname: Biddle
mesh_terms: D000222:Adaptation, Physiological / Q000502:physiology; D001812:Blood-Brain Barrier / Q000502:physiology; D001833:Body Temperature Regulation / Q000502:physiology; D015984:Causality; D016207:Cytokines / Q000502:physiology; D005334:Fever / Q000209:etiology* / Q000378:metabolism / Q000503:physiopathology* / Q000517:prevention & control; D006706:Homeostasis / Q000502:physiology; D006801:Humans; D007031:Hypothalamus / Q000503:physiopathology; D009446:Neurobiology; D011183:Postoperative Complications / Q000209:etiology; D011451:Prostaglandin-Endoperoxide Synthases / Q000502:physiology; D011453:Prostaglandins / Q000502:physiology; D011749:Pyrogens
chemical_list: D016207:Cytokines; D011453:Prostaglandins; D011749:Pyrogens; D011451:Prostaglandin-Endoperoxide Synthases