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

Author(s)

Soares, Denis Melo ^[1] ; Figueiredo, Maria Jose ^[1] ; Martins, Juliano Manvailer ^[1] ; Machado, Renes Resende ^[1] ; Kanashiro, Alexandre ^[1] ; Malvar, David do Carmo ^[1] ; Pessini, Andrea Carla ^[1] ; Roth, Joachim ^[2] ; Petto Souza, Gloria Emilia ^[1]

Affiliation

^[1] Fac Ciencias Farmaceut Ribeirao Preto, Farmacol Lab, BR-14040903 Ribeirao Preto, SP - Brazil

^[2] Univ Giessen, Dept Vet Physiol, Fac Vet Med, D-35392 Giessen - Germany

• Document type: Journal article
• Source: Brain Research; v. 1269, p. 54-60, MAY 7 2009.
• Web of Science Citations: 12

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)-1 alpha (synonym CCL3) also induces a prostaglandin independent fever, the aim of the present study was to investigate a possible participation of CCL3/MIP-1 alpha 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; S, 50 or 100 mu g kg(-1), i.v.) or CCL3/MIP-1 alpha (500 pg, i.c.v.). Both doses of anti-CCL3 did not change the basal temperature but abolished the fever induced by CCL3/MIP-1 alpha. 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 mu g) or ET-1 (1 pmol). Bosentan, a non-selective ET(A/B) receptors antagonist (10 mu g kg(-1), i.v.), reduced the fever induced by LPS but not that induced by CCL3/MIP-1 alpha. in contrast, alpha-helical CRF(9-41) (a non-selective CRF R1/R2 receptor antagonist; 25 mu g injected i.c.v.) reduced CCL3/MIP-1 alpha-induced fever. In conclusion, the present results indicate that: i) CCL3/MIP-1 alpha 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. (C) 2009 Elsevier B.V. All rights reserved. (AU)

• FAPESP's process: 97/09837-6 - Mechanisms and mediators involved in the integration of fever and inflammatory responses
• Grantee: Glória Emília Petto de Souza
• Support Opportunities: Research Projects - Thematic Grants