title: Evidence of substance P autocrine circuitry that involves TNF-α, IL-6, and PGE2 in endogenous pyrogen-induced fever.
abstract: Substance P (SP) is involved in fever that is induced by lipopolysaccharide (LPS) but not by interleukin-1β or macrophage inflammatory protein-1α. Intracerebroventricular (i.c.v.) administration of the neurokinin-1 (NK1) receptor antagonist SR140333B in rats reduced fever that was induced by an i.c.v. injection of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), prostaglandin E2 (PGE2), corticotropin-releasing factor (CRF), endothelin-1 (ET-1), and morphine (MOR). Furthermore, an i.c.v. injection of SP induced a febrile response that was inhibited by indomethacin concomitant with an increase in PGE2 levels in cerebrospinal fluid. Lipopolysaccharide and PGE2 caused higher expression and internalization of NK1 receptors in the hypothalamus which were prevented by SR140333B. These data suggest that SP is an important mediator of fever, in which it induces a prostaglandin-dependent response and is released after TNF-α, IL-6, PGE2, CRF, endogenous opioids, and ET-1.
authors.affiliation: Department of Pharmacology, Federal University of Paraná, P.O. Box 19031, Curitiba, PR 81540-970, Brazil.
authors.forename: Haissa Oliveira
authors.initials: HO
authors.lastname: Brito
authors.affiliation: Department of Pharmacology, Federal University of Paraná, P.O. Box 19031, Curitiba, PR 81540-970, Brazil.
authors.forename: Felipe L
authors.initials: FL
authors.lastname: Barbosa
authors.affiliation: Department of Pharmacology, Federal University of Paraná, P.O. Box 19031, Curitiba, PR 81540-970, Brazil.
authors.forename: Renata Cristiane Dos
authors.initials: RCD
authors.lastname: Reis
authors.affiliation: Department of Pharmacology, Federal University of Paraná, P.O. Box 19031, Curitiba, PR 81540-970, Brazil.
authors.forename: Daniel
authors.initials: D
authors.lastname: Fraga
authors.affiliation: Department of Cell Biology, Federal University of Paraná, P.O. Box 19031, Curitiba, PR 81540-970, Brazil.
authors.forename: Beatriz S
authors.initials: BS
authors.lastname: Borges
authors.affiliation: Department of Cell Biology, Federal University of Paraná, P.O. Box 19031, Curitiba, PR 81540-970, Brazil.
authors.forename: Celia R C
authors.initials: CRC
authors.lastname: Franco
authors.affiliation: Department of Pharmacology, Federal University of Paraná, P.O. Box 19031, Curitiba, PR 81540-970, Brazil. Electronic address: aleksander@ufpr.br.
authors.forename: Aleksander Roberto
authors.initials: AR
authors.lastname: Zampronio
mesh_terms: D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology; D001831:Body Temperature / Q000187:drug effects; D003346:Corticotropin-Releasing Hormone / Q000494:pharmacology; D015232:Dinoprostone / Q000134:cerebrospinal fluid*; D005334:Fever / Q000139:chemically induced* / Q000517:prevention & control*; D005786:Gene Expression Regulation / Q000187:drug effects; D007031:Hypothalamus / Q000187:drug effects / Q000378:metabolism; D007213:Indomethacin / Q000494:pharmacology; D015850:Interleukin-6 / Q000008:administration & dosage / Q000378:metabolism; D008297:Male; D009020:Morphine / Q000494:pharmacology; D011134:Polysaccharides / Q000633:toxicity; D011749:Pyrogens; D051381:Rats; D017208:Rats, Wistar; D018040:Receptors, Neurokinin-1 / Q000378:metabolism; D013373:Substance P / Q000378:metabolism / Q000494:pharmacology*; D013997:Time Factors; D014326:Tropanes / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism / Q000494:pharmacology
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D015850:Interleukin-6; D011134:Polysaccharides; D011749:Pyrogens; D018040:Receptors, Neurokinin-1; C526005:SR140333B; D014326:Tropanes; D014409:Tumor Necrosis Factor-alpha; D013373:Substance P; D009020:Morphine; D003346:Corticotropin-Releasing Hormone; D015232:Dinoprostone; D007213:Indomethacin
keywords: Corticotroin-releasing factor; Cytokines; Endogenous opioids; Endothelin-1; Prostaglandin; Substance P