THE EFFECT OF SALMETEROL AND NIMESULIDE ON CHEMOTAXIS AND SYNTHESIS OF PAF AND LTC(4) BY HUMAN EOSINOPHILS

Salmeterol is a long-acting beta(2)-adrenoceptor agonist, with several antiasthma properties, Nimesulide is a nonsteroidal anti-inflammatory drug, supposed to act by inhibition of phosphodiesterase type IV, Thi s might indicate that the effects of both drugs are mediated by an inc rease in cyclic adenosine monophosphate (cAMP), For salmeterol, it has been shown that it inhibits the influx of eosinophils into the lungs of guinea-pigs after platelet-activating factor (PAF) challenge, sugge sting an effect of cAMP on eosinophil migration, For neutrophils, it h as been shown that PAF synthesis is inhibited by cAMP. In the present study, we have, therefore, measured the effect of salmeterol and nimes ulide on two important human eosinophil functions: chemotaxis; and syn thesis of PAF and leukotriene C-4 (LTC(4)). Both drugs were found to b e inhibitors of the chemotactic responses of human eosinophils, Howeve r, at comparable concentrations, only nimesulide was able to inhibit t he synthesis of PAF and LTC(4) in activated eosinophils. These results indicate that although the effects of both drugs are thought to be me diated by an increase in cyclic adenosine monophosphate, they have dif ferential effects on eosinophil chemotaxis and synthesis of lipid medi ators.