title: Fever and anapyrexia in systemic inflammation: intracellular signaling by cyclic nucleotides.
abstract: During systemic inflammation, body temperature is either increased (fever) or decreased (anapyrexia). Either response depends on the dose of the inflammatory agent, e.g., lipopolysaccharide (LPS), and on the ambient temperature. Under thermoneutrality, LPS always produces fever; under subthermoneutral conditions, LPS evokes fever at lower doses and anapyrexia at higher doses. Because of the diagnostic and adaptive values of these responses, understanding their mechanisms is of interest. Recently, the intracellular mechanisms that occur in the preoptic region (PO), the thermointegrative site of the brain, to produce fever and anapyrexia have begun to be clarified. In response to febrigenic doses of LPS, an increased production of prostaglandin E2 and an inhibition of nitric oxide synthesis produce fever respectively by decreasing the intracellular content of cyclic AMP (cAMP) and cyclic GMP (cGMP) in the PO. Although the role of preoptic cAMP and cGMP has not been directly assessed in the anapyrexia induced by LPS, it has been studied in that induced by hypoxia. The likeness between the thermoregulatory responses to hypoxia and to a high dose of LPS suggests that they may have similar mechanisms. In contrast to fever, hypoxia-induced anapyrexia seems to be mediated by a simultaneous increase in the levels of cAMP and cGMP in the PO as the result of an enhanced production and/or release of serotonin and nitric oxide, respectively. This article reviews the recent advances in the understanding of the role of preoptic cAMP and cGMP signaling cascades in fever and anapyrexia.
authors.affiliation: Systemic Inflammation Laboratory, Trauma Research, St. Joseph's Hospital and Medical Center, Phoenix, AZ 85013, USA. a2steiner@chw.edu
authors.forename: Alexandre A
authors.initials: AA
authors.lastname: Steiner
authors.forename: Luiz G S
authors.initials: LG
authors.lastname: Branco
mesh_terms: D000818:Animals; D000242:Cyclic AMP / Q000502:physiology*; D006152:Cyclic GMP / Q000502:physiology*; D005334:Fever / Q000209:etiology / Q000378:metabolism*; D006801:Humans; D007249:Inflammation / Q000209:etiology / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology*
chemical_list: D000242:Cyclic AMP; D006152:Cyclic GMP