Differential effects of salbutamol and salmeterol on human eosinophil responses

In the treatment of bronchial asthma, salmeterol is believed to have a greater anti-inflammatory activity than salbutamol. To determine whether the comparative effects of these drugs on eosinophil function are the basis of their differential anti-inflammatory properties, we studied the effect of the two drugs on interleukin-5 (IL-5) and 1-alkyl-2-acetyl-sn-glycero-3-phosphocholine (PAF)-induced O2- release and adherence to fibronectin-coated plates, as well as the C5a- and N-formylmethionyl-leucyl-phenylalanine (FMLP)-induced degranulation of purified human blood eosinophils in vitro. Salmeterol significantly inhibited IL-5-induced O2- release in a concentration-dependent manner with an IC50 of 2.2 X 10(-6) M (95% CI, 1.6-2.7 X 10(-6) M) and a maximal inhibition of about 70%. In contrast, salbutamol had no significant effect even at 10(-5) M. Both drugs significantly inhibited PAF-induced O2- generation, but salmeterol was approximately 20 times more potent than salbutamol. Salmeterol also significantly inhibited adherence induced by both IL-5 and PAF, whereas salbutamol had no significant effect on adherence induced by both agents. Both drugs failed to block C5a-induced eosinophil peroxidase release, whereas for FMLP-induced release, salbutamol, but not salmeterol, produced significant inhibition. Unlike salbutamol, all the actions of salmeterol were independent of beta-2 adrenoceptors. These results confirm that human eosinophils can be modulated directly by beta-2 adrenoceptor agonists, but that salmeterol 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 O2- release and adherence, rather than degranulation.