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Neutralization of macrophage inflammatory protein-2 blocks the febrile response induced by lipopolysaccharide in rats
Authors:Eva Tavares  Maria L Ojeda  Rosario Maldonado  Francisco J Miano
Institution:

aResearch Unit, Laboratory for Clinical and Experimental Pharmacology, Valme University Hospital, Seville 41014, Spain

bDepartment of Pharmacology, Radiology and Paediatrics, School of Medicine, University of Seville, Seville 41009, Spain

Abstract:1. This study was aimed to test the hypothesis that macrophage inflammatory protein-2 (MIP-2), a powerful chemotactic cytokine for neutrophils, plays a role in bacterial endotoxin fever.

2. The effect of specific anti-rat MIP-2 antibodies on lipopolysaccharide (LPS)-induced fever was tested. Intraperitoneal injection of LPS resulted in a biphasic fever and a significant increase in serum MIP-2 and prostaglandin (PG) E2 levels which correlated with the start of fever. Intraperitoneal anti-MIP-2 (500 μg/kg) did not affect the body core temperature of unrestrained rats, but markedly attenuated LPS-induced fever.

3. Treatment with the cyclooxygenase inhibitor ibuprofen (10 mg/kg) resulted in a significant attenuation of LPS-induced fever and a significant decrease of MIP-2 and PGE2 production.

4. These results indicate that LPS fever in rats is, at least, in part dependent on mechanisms involving neutrophils chemotaxis, and that MIP-2 may be an important mediator in the genesis of fever via prostaglandin-dependent pathways.

Keywords:Fever  Ibuprofen  MIP-2  PGE2  Rats
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