title: Central endothelin ET(B) receptors mediate IL-1-dependent fever induced by preformed pyrogenic factor and corticotropin-releasing factor in the rat.
abstract: Blockade of central endothelin ET(B) receptors inhibits fever induced by LPS in conscious rats. The contribution of ET(B) receptor-mediated mechanisms to fever triggered by intracerebroventricular IL-6, PGE2, PGF(2alpha), corticotropin-releasing factor (CRF), and preformed pyrogenic factor derived from LPS-stimulated macrophages (PFPF) was examined. The influence of natural IL-1 receptor antagonist or soluble TNF receptor I on endothelin (ET)-1-induced fever was also assessed. The selective ET(B) receptor antagonist BQ-788 (3 pmol icv) abolished fever induced by intracerebroventricular ET-1 (1 pmol) or PFPF (200 ng) and reduced that caused by ICV CRF (1 nmol) but not by IL-6 (14.6 pmol), PGE2 (1.4 nmol), or PGF(2alpha) (2 nmol). CRF-induced fever was also attenuated by bosentan (dual ET(A)/ET(B) receptor antagonist; 10 mg/kg iv) but unaffected by BQ-123 (selective ET(A) receptor antagonist; 3 pmol icv). alpha-Helical CRF(9-41) (dual CRF1/CRF2 receptor antagonist; 6.5 nmol icv) attenuated fever induced by CRF but not by ET-1. Human IL-1 receptor antagonist (9.1 pmol) markedly reduced fever to IL-1beta (180 fmol) or ET-1 and attenuated that caused by PFPF or CRF. Murine soluble TNF receptor I (23.8 pmol) reduced fever to TNF-alpha (14.7 pmol) but not to ET-1. The results of the present study suggest that PFPF and CRF recruit the brain ET system to cause ET(B) receptor-mediated IL-1-dependent fever.
authors.affiliation: Laboratório de Farmacologia, Faculdade de Ciências Farmacêuticas de Ribeirão Preto, Universidade de São Paulo, Av. do Café, s/n-Campus USP 14040-903 Ribeirão Preto, SP, Brazil.
authors.forename: Aline S C
authors.initials: AS
authors.lastname: Fabricio
authors.forename: Giles A
authors.initials: GA
authors.lastname: Rae
authors.forename: Aleksander R
authors.initials: AR
authors.lastname: Zampronio
authors.forename: Pedro
authors.initials: P
authors.lastname: D'Orléans-Juste
authors.forename: Glória E P
authors.initials: GE
authors.lastname: Souza
mesh_terms: D000818:Animals; D001831:Body Temperature; D003346:Corticotropin-Releasing Hormone / Q000494:pharmacology*; D015237:Dinoprost / Q000378:metabolism; D015232:Dinoprostone / Q000378:metabolism; D065131:Endothelin B Receptor Antagonists; D000068800:Etanercept; D005334:Fever / Q000139:chemically induced / Q000503:physiopathology*; D007074:Immunoglobulin G / Q000494:pharmacology; D053590:Interleukin 1 Receptor Antagonist Protein; D007375:Interleukin-1 / Q000378:metabolism*; D008070:Lipopolysaccharides / Q000494:pharmacology; D008297:Male; D010446:Peptide Fragments / Q000494:pharmacology; D011749:Pyrogens / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D044023:Receptor, Endothelin B / Q000378:metabolism*; D018124:Receptors, Tumor Necrosis Factor; D047888:Receptors, Tumor Necrosis Factor, Type I / Q000378:metabolism; D012795:Sialoglycoproteins / Q000378:metabolism
chemical_list: D065131:Endothelin B Receptor Antagonists; C507763:IL1RN protein, human; D007074:Immunoglobulin G; D053590:Interleukin 1 Receptor Antagonist Protein; D007375:Interleukin-1; D008070:Lipopolysaccharides; D010446:Peptide Fragments; D011749:Pyrogens; D044023:Receptor, Endothelin B; D018124:Receptors, Tumor Necrosis Factor; D047888:Receptors, Tumor Necrosis Factor, Type I; D012795:Sialoglycoproteins; D003346:Corticotropin-Releasing Hormone; C045089:corticotropin releasing hormone (9-41); D015237:Dinoprost; D015232:Dinoprostone; D000068800:Etanercept