Endogenous antipyretics.
Fever is the hallmark of the stereotyped host response to microbial infection, although it is just one of a number of high-risk strategies employed by the infected host to clear itself of invading pathogens. The febrile response is accompanied by activation of multiple endogenous antipyretic systems that serve to suppress its magnitude or duration. These include neuroactive substances of neural and humoral origin, some of which (e.g., glucocorticoids, melanocortins, and IL-10) have broad-ranging anti-inflammatory actions. Glucocorticoids, vasopressin, and melanocortins appear to exert their antipyretic effects by acting on receptors within the brain, but beyond this the mechanisms involved are unknown. It is hypothesized, but not proven, that endogenous antipyretic systems protect the host against the destructive consequences of unchecked fever. Importantly, pharmacological blockade of the actions of endogenous antipyretic systems increases fevers of even low to moderate intensity. Therefore, in addition to protecting against catastrophic consequences of high fever, endogenous antipyretic systems seem to play a fundamental physiological role in determining the normal course of fever. Elucidating the neural and biochemical mechanisms involved in suppression of fever by physiological antipyretic systems will yield a rich benefit, both by advancing the basic understanding of host defense strategies, and by permitting the design of novel antipyretic and anti-inflammatory strategies for therapeutic intervention in human disease.
Tatro
J B
JB
Division of Endocrinology, Diabetes, Metabolism and Molecular Medicine, Department of Medicine, Tupper Research Institute, Tufts University School of Medicine and New England Medical Center, Boston, MA 02111, USA. jtatro@lifespan.org
D000324:Adrenocorticotropic Hormone / Q000378:metabolism; D018712:Analgesics, Non-Narcotic / Q000378:metabolism*; D017305:Annexin A1 / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism; D005334:Fever / Q000378:metabolism*; D005938:Glucocorticoids / Q000378:metabolism; D006801:Humans; D009479:Neuropeptides / Q000378:metabolism; D014667:Vasopressins / Q000378:metabolism; D000521:alpha-MSH / Q000378:metabolism
D018712:Analgesics, Non-Narcotic; D017305:Annexin A1; D016207:Cytokines; D005938:Glucocorticoids; D009479:Neuropeptides; D014667:Vasopressins; D000521:alpha-MSH; D000324:Adrenocorticotropic Hormone