The effect of salmeterol and nimesulide on chemotaxis and synthesis of PAF and LTC4 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. This might indicate that the effects of both drugs are mediated by an increase 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, suggesting an effect of cAMP on eosinophil migration. For neutrophils, it has been shown that PAF synthesis is inhibited by cAMP. In the present study, we have, therefore, measured the effect of salmeterol and nimesulide on two important human eosinophil functions: chemotaxis; and synthesis of PAF and leukotriene C4 (LTC4). Both drugs were found to be inhibitors of the chemotactic responses of human eosinophils. However, at comparable concentrations, only nimesulide was able to inhibit the synthesis of PAF and LTC4 in activated eosinophils. These results indicate that although the effects of both drugs are thought to be mediated by an increase in cyclic adenosine monophosphate, they have differential effects on eosinophil chemotaxis and synthesis of lipid mediators.
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Central Laboratory of the Netherlands Red Cross Blood Transfusion Service, University of Amsterdam, The Netherlands.
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Knol
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Verhoeven
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Roos
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D000318:Adrenergic beta-Agonists / Q000494:pharmacology*; D000420:Albuterol / Q000031:analogs & derivatives* / Q000494:pharmacology; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D001249:Asthma / Q000188:drug therapy* / Q000276:immunology*; D002633:Chemotaxis / Q000187:drug effects*; D015936:Complement C5a / Q000378:metabolism; D000242:Cyclic AMP / Q000378:metabolism; D004804:Eosinophils / Q000187:drug effects* / Q000276:immunology*; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology; D006168:Guinea Pigs; D006801:Humans; D017997:Leukotriene C4 / Q000096:biosynthesis*; D010972:Platelet Activating Factor / Q000096:biosynthesis*; D000068299:Salmeterol Xinafoate; D013449:Sulfonamides / Q000494:pharmacology*
D000318:Adrenergic beta-Agonists; D000894:Anti-Inflammatory Agents, Non-Steroidal; D010972:Platelet Activating Factor; D013449:Sulfonamides; D017997:Leukotriene C4; D000068299:Salmeterol Xinafoate; D015936:Complement C5a; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D000242:Cyclic AMP; D000420:Albuterol; C012655:nimesulide