Nimesulide Inhibits Platelet-Activating Factor Synthesis in Activated Human Neutrophils

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Abstract
In an inflammatory locus, products of activated neutrophils may be toxic both to the microorganisms to be eliminated and to the surrounding tissue. In several models of inflammation, nimesulide possesses marked anti-inflammatory properties. The present study was undertaken to further investigate the effects of nimesulide on the activation of human neutrophils. Nimesulide caused a concentration-dependent inhibition of the homotypic aggregation of neutrophils upon activation with the receptor agonist formyl-Met-Leu-Phe. Likewise, nimesulide inhibited the heterotypic interaction of human neutrophils with endothelial cells in suspension. Since both these responses are mediated through activation of the integrin CD11b/CD18 on the neutrophil surface, we conclude that nimesulide interferes with the signal transduction leading to this activation. We also observed a strong inhibition of platelet-activating factor (PAF) synthesis by activated neutrophils in the presence of nimesulide. PAF has been implicated as an intercellular messenger in the diapedesis of neutrophils across endothelial cell monolayers after treatment with cytokines and in the activation of eosinophils.