CCL3/MIP-1α is not involved in the LPS-induced fever and its pyrogenic activity depends on CRF

• Published in: Brain research 2009-05, Vol.1269, p.54-60
• Main Authors: Soares, Denis Melo, Figueiredo, Maria José, Martins, Juliano Manvailer, Machado, Renes Resende, Kanashiro, Alexandre, Malvar, David do Carmo, Pessini, Andréa Carla, Roth, Joachim, Souza, Glória Emília Petto
• Format: Article
• Language: English
• Subjects: Animals; Antibodies, Monoclonal - pharmacology; Antihypertensive Agents - pharmacology; Biological and medical sciences; CCL3; Chemokine CCL3 - immunology; Chemokine CCL3 - pharmacology; Chemokines; Corticotropin-Releasing Hormone - metabolism; Corticotropin-Releasing Hormone - pharmacology; Drug Interactions; Endothelin-1 - metabolism; Escherichia coli; Fever; Fever - chemically induced; Fever - immunology; Fundamental and applied biological sciences. Psychology; Injections, Intraventricular; Lipopolysaccharides - pharmacology; LPS; Macrophages - immunology; Male; Mice; MIP-1α; Neurology; Peptide Fragments - metabolism; Peptide Fragments - pharmacology; Prostaglandins; Rats; Rats, Wistar; Recombinant Proteins - immunology; Recombinant Proteins - pharmacology; Sulfonamides - pharmacology; Thermoregulation. Hibernation. Estivation. Ecophysiology and environmental effects; Vertebrates: anatomy and physiology, studies on body, several organs or systems
• ISSN: 0006-8993; 1872-6240
• DOI: 10.1016/j.brainres.2009.03.003

Abstract The fever induced by lipopolysaccharide (LPS) depends on both prostaglandin-dependent and -independent pathways. One of the prostaglandin-independent pathways is sequentially orchestrated by pre-formed pyrogenic factor derived from LPS-stimulated macrophages (PFPF), corticotrophin releasing factor (CRF), endothelin-1 (ET-1) and interleukin-1 (IL-1). As macrophage-inflammatory-protein (MIP)-1α (synonym CCL3) also induces a prostaglandin independent fever, the aim of the present study was to investigate a possible participation of CCL3/MIP-1α within the prostaglandin-independent pathway of LPS-induced fever which depends on PFPF, CRF and ET-1. Therefore, rats received intracerebroventricular (i.c.v.) pre-treatment with anti-CCL3 monoclonal antibody (1 and 5 ng) at 1 h and 15 min before injection of LPS (lipopolysaccharide from E. coli ; 5, 50 or 100 μg kg − 1 , i.v.) or CCL3/MIP-1α (500 pg, i.c.v.). Both doses of anti-CCL3 did not change the basal temperature but abolished the fever induced by CCL3/MIP-1α. When given at the higher dose, anti-CCL3 did not influence the fever induced by i.v. injection of different doses of LPS, or i.c.v. administration of PFPF (200 ng), CRF (3 μg) or ET-1 (1 pmol). Bosentan, a non-selective ETA/B receptors antagonist (10 μg kg − 1 , i.v.), reduced the fever induced by LPS but not that induced by CCL3/MIP-1α. In contrast, α-helical CRF9−41 (a non-selective CRF R1/R2 receptor antagonist; 25 μg injected i.c.v.) reduced CCL3/MIP-1α-induced fever. In conclusion, the present results indicate that: i ) CCL3/MIP-1α is not an endogenous mediator of LPS-induced fever; ii ) it is even not involved in the prostaglandin-independent pathway of the LPS-fever cascade and iii ) its pyrogenic activity depends on synthesis/release of CRF.