Abstract
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.
Footnotes
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Send reprint requests to: Dr. Charles I Ezeamuzie, Department of Pharmacology and Toxicology, Faculty of Medicine, Kuwait University, P.O. Box 24923, Safat, 13110, Kuwait.
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↵1 This work was supported by grant MR 030 from Research Administration, Kuwait University.
- Abbreviations:
- IL-5
- interlukin-5
- PAF
- 1-alkyl-2-acetyl-sn-glycero-3-phosphocholine
- C5a
- complement fragment 5a
- O2[sup]−
- superoxide anion
- EPO
- eosinophil peroxidase
- FMLP
- N-formylmethionyl-leucyl-phenylalanine
- ECP
- eosinophil cationic protein
- MBP
- major basic protein
- EDN
- eosinophil-derived neurotoxin
- PBS
- phosphate-buffered saline
- LTB4
- leukotriene B4
- BSA
- bovine serum albumin
- SOD
- superoxide dismutase
- DMSO
- dimethyl sulfoxide
- CB
- cytochalasin B
- PLC
- phospholipase C
- PKA
- protein kinase A
- PKC
- protein kinase C
- IC50
- concentration achieving 50% inhibition
- HEPES
- N-[2-hydroxyethyl]piperazine-N′-[2-ethanesulphonic acid]
- OPD
- O-phenylenediamine
- ICI 118551
- erythro-(±)-1-(7-methylindan-4-yloxy)-3-isopropylaminobutan-2-ol hydrochloride
- CI
- confidence interval
- ANOVA
- analysis of variance
- Received May 6, 1997.
- Accepted September 23, 1997.
- The American Society for Pharmacology and Experimental Therapeutics
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