DIFFERENTIAL-EFFECTS OF SALBUTAMOL AND SALMETEROL ON HUMAN EOSINOPHILRESPONSES

In the treatment of bronchial asthma, salmeterol is believed to have a greater anti-inflammatory activity than salbutamol. To determine whet her the comparative effects of these drugs on eosinophil function are the basis of their differential anti-inflammatory properties, we studi ed the effect of the two drugs on interleukin-5 (IL-5) and 1-alkyl-2-a cetyl-sn-glycero-3-phosphocholine (PAF)-induced O-2(-) release and adh erence to fibronectin-coated plates, as well as the C5a- and N-formylm ethionyl-leucyl-phenylalanine (FMLP)-induced degranulation of purified human blood eosinophils in vitro. Salmeterol significantly inhibited IL-5-induced O-2(-) release in a concentration-dependent manner with a n IC50 of 2.2 x 10(-6) M (95% CI, 1.6-2.7 x 10(-6) M) and a maximal in hibition of about 70%. In contrast, salbutamol had no significant effe ct even at 10(-5) M. Both drugs significantly inhibited PAF-induced O- 2(-) generation, but salmeterol was approximately 20 times more potent than salbutamol. Salmeterol also significantly inhibited adherence in duced by both IL-5 and PAF, whereas salbutamol had no significant effe ct on adherence induced by both agents. Both drugs failed to block C5a -induced eosinophil peroxidase release, whereas for FMLP-induced relea se, salbutamol, but not salmeterol, produced significant inhibition. U nlike salbutamol, all the actions of salmeterol were independent of be ta-2 adrenoceptors. These results confirm that human eosinophils can b e modulated directly by beta-2 adrenoceptor agonists, but that salmete rol and salbutamol have differential effects which depend on both the stimulus used and the response being measured and that the reportedly greater in vivo anti-inflammatory effect of salmeterol may reflect its superior ability to inhibit eosinophil O-2(-) release and adherence, rather than degranulation.