Cytokines, but not corticotropin-releasing factor and endothelin-1, participate centrally in the febrile response in zymosan-induced arthritis in rats

• Published in: Brain research Vol. 1610; pp. 12 - 19
• Main Authors: Kanashiro, Alexandre, Figueiredo, Maria J, Malvar, David do C, Souza, Glória E.P
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 12.06.2015
• Subjects: Animals; Arthritis - physiopathology; Body Temperature - physiology; Corticotropin-releasing factor; Corticotropin-Releasing Hormone - metabolism; Cytokines; Cytokines - metabolism; Disease Models, Animal; Endothelin; Endothelin-1 - metabolism; Fever; Fever - physiopathology; Hyperalgesia - physiopathology; Male; Neurology; Rats, Wistar; Zymosan; Zymosan-induced arthritis; IL-1 receptor antagonist; PGE 2; TNF; LPS; corticotropin-releasing factor; i.pl; analysis of variance; ANOVA; intra-plantar; intracerebroventricular; prostaglandin E 2; interleukin; i.a; anti-rat IL-6 monoclonal antibody; intra-articular; IL; IL-1ra; Cytokines; artificial cerebrospinal fluid; Fever; ET; endothelin; sTNFRI; tumor necrosis factor; CRF; soluble TNF receptor I; aCSF; i.c.v; SEM; standard error of the mean; lipopolysaccharide; Zymosan-induced arthritis; AbIL-6; PGE2; Endothelin; Corticotropin-releasing factor
• ISSN: 0006-8993; 1872-6240
• DOI: 10.1016/j.brainres.2015.03.036

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.