title: Cytokines, but not corticotropin-releasing factor and endothelin-1, participate centrally in the febrile response in zymosan-induced arthritis in rats.
abstract: Recent literature has revealed that centrally generated prostaglandins participate in the febrile response in zymosan-induced arthritis in rats. However, it is not clear whether other centrally acting pyrogenic mediators such as cytokines, endothelins (ETs), and the corticotropin-releasing factor (CRF) contribute to the febrile response in this model. In the present study, rats were pretreated with intracerebroventricular (i.c.v.) injections of soluble TNF receptor I (sTNFRI), recombinant IL-1 receptor antagonist (IL-1ra), anti-rat IL-6 monoclonal antibody (AbIL-6), α-helical CRF9-41 (a nonselective CRF1/CRF2 receptor antagonist), BQ-123 (an ETA receptor antagonist), BQ-788 (an ETB receptor antagonist), and artificial cerebrospinal fluid (aCSF, control) prior to an intra-articular zymosan (4 mg) injection. Rectal temperatures were measured with a telethermometer. The administration of IL-1ra (200 µg), sTNFRI (500 ng), and AbIL-6 (5 µg) attenuated body temperature elevations after a zymosan injection. The administration of BQ-788 (3 pmol), BQ-123 (3 pmol), and α-helical CRF9-41 (25 µg) did not affect the zymosan-induced febrile response. All the compounds used to pretreat the animals did not significantly alter their basal body temperatures. Together, the results here demonstrate that the febrile response in zymosan-induced arthritis in rats depends on the centrally acting pyrogenic cytokines TNF-α, IL-1β, and IL-6, but does not depend on either CRF or ET-1.
authors.affiliation: Laboratory of Pharmacology, Department of Physics and Chemistry, School of Pharmaceutical Sciences of Ribeirão Preto, University of São Paulo, Av. do Café s/n, Ribeirão Preto 14040-903, SP, Brazil.
authors.forename: Alexandre
authors.initials: A
authors.lastname: Kanashiro
authors.affiliation: Laboratory of Pharmacology, Department of Physics and Chemistry, School of Pharmaceutical Sciences of Ribeirão Preto, University of São Paulo, Av. do Café s/n, Ribeirão Preto 14040-903, SP, Brazil.
authors.forename: Maria J
authors.initials: MJ
authors.lastname: Figueiredo
authors.affiliation: Laboratory of Pharmacology, Department of Physiologic Sciences, Federal Rural University of Rio de Janeiro, BR 465/Km 07, Seropédica 23890-000, RJ, Brazil.
authors.forename: David do C
authors.initials: Ddo C
authors.lastname: Malvar
authors.affiliation: Laboratory of Pharmacology, Department of Physics and Chemistry, School of Pharmaceutical Sciences of Ribeirão Preto, University of São Paulo, Av. do Café s/n, Ribeirão Preto 14040-903, SP, Brazil. Electronic address: gepsouza@fcfrp.usp.br.
authors.forename: Glória E P
authors.initials: GE
authors.lastname: Souza
mesh_terms: D000818:Animals; D001168:Arthritis / Q000503:physiopathology*; D001831:Body Temperature / Q000502:physiology; D003346:Corticotropin-Releasing Hormone / Q000378:metabolism*; D016207:Cytokines / Q000378:metabolism*; D004195:Disease Models, Animal; D019332:Endothelin-1 / Q000378:metabolism*; D005334:Fever / Q000503:physiopathology*; D006930:Hyperalgesia / Q000503:physiopathology; D008297:Male; D017208:Rats, Wistar; D015054:Zymosan
chemical_list: D016207:Cytokines; D019332:Endothelin-1; D015054:Zymosan; D003346:Corticotropin-Releasing Hormone
keywords: Corticotropin-releasing factor; Cytokines; Endothelin; Fever; Zymosan-induced arthritis