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Vol. 284, Issue 1, 25-31, 1998
Department of Pharmacology and Toxicology, Faculty of Medicine,
Kuwait University, Kuwait
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 × 10
6 M (95% CI, 1.6-2.7 × 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.
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