Inhibition of Neutrophil Respiratory Burst by Nimesulide

Abstract

Activation of NADPH oxidase and superoxide anion release in human neutrophils has been shown to be dependent on Na+/H+ exchange, and inhibition of intracellular alkalinisation has been proposed as a mechanism of action for some anti-inflammatory drugs. The effect of nimesulide, a novel nonsteroidal anti-inflammatory drug, on intracellular pH (pHi) regulation by the Na+/H+ antiport in human neutrophils was examined using the pH-sensitive fluorescent probe 2,7-biscarboxyethyl-5(6)-carboxyfluorescein (BCECF), When stimulated by formylmethionylleucyl-phenylalanine (fMLP) or phorbol-12-myristate-13-acetate (PM A), neutrophils displayed changes in pHi consisting of an initial acidification followed by a sustained alkalinising phase indicative of antiport activation. Nimesulide did not change the pHi of resting neutrophils and did not affect the pHi response to stimulation, It is concluded that the anti-inflammatory effect of nimesulide is not directly linked to interactions with the Na+/H+ antiport or other pathways affecting the regulation of pHi.