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

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; 5, 50 or 100 microg 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 microg) or ET-1 (1 pmol). Bosentan, a non-selective ET(A/B) receptors antagonist (10 microg 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 microg 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.

• Authors: Denis Melo Soares, Maria José Figueiredo, Juliano Manvailer Martins, Renes Resende Machado, Alexandre Kanashiro, David do Carmo Malvar, Andréa Carla Pessini, Joachim Roth, Glória Emília Petto Souza
• Journal: Brain research (Brain Res) Vol. 1269 Pg. 54-60 (May 07 2009) ISSN: 1872-6240 [Electronic] Netherlands
• PMID: 19285486 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antibodies, Monoclonal
• Antihypertensive Agents
• Ccl3 protein, mouse
• Chemokine CCL3
• Endothelin-1
• Lipopolysaccharides
• Peptide Fragments
• Recombinant Proteins
• Sulfonamides
• Corticotropin-Releasing Hormone
• Bosentan

Topics

• Animals
• Antibodies, Monoclonal (pharmacology)
• Antihypertensive Agents (pharmacology)
• Bosentan
• Chemokine CCL3 (immunology, pharmacology)
• Corticotropin-Releasing Hormone (metabolism, pharmacology)
• Drug Interactions
• Endothelin-1 (metabolism)
• Fever (chemically induced, immunology)
• Injections, Intraventricular
• Lipopolysaccharides (pharmacology)
• Macrophages (immunology)
• Male
• Mice
• Peptide Fragments (metabolism, pharmacology)
• Rats
• Rats, Wistar
• Recombinant Proteins (immunology, pharmacology)
• Sulfonamides (pharmacology)