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Int Arch Allergy Immunol. 2006;139(1):1-8. Epub 2005 Nov 2.

Differential effects of short-acting beta2-agonists on human granulocyte functions.

Author information

1
Department of Pediatrics, Shinshu University School of Medicine, Matsumoto, Japan.

Abstract

BACKGROUND:

beta2-Adrenergic agonists play a pivotal role in the management of bronchial asthma. Although the major effect of short-acting beta2-agonists on the airway is relaxation of smooth muscles, they may also have several effects on surrounding immunomodulatory cells.

METHODS:

We examined whether widely used short-acting beta2-agonists differ in their ability to modulate granulocyte functions, such as superoxide anion (O2-) production and degranulation.

RESULTS:

Procaterol (PC), a full agonist, significantly inhibited both O2- production by granulocytes (neutrophils and eosinophils) and their degranulation at the clinically relevant concentrations, whereas salbutamol and tulobuterol (partial agonists) showed smaller effects. PC inhibited N-formyl methionyl-leucyl-phenylalanine-induced O2- production and peroxidase release, but failed to inhibit responses induced by phorbol 12-myristate 13-acetate and/or opsonized zymosan. Exposure to 5 x 10(-8)M PC for 120 min resulted in approximately 50% inhibition of O2- production and degranulation of neutrophils. The effects of beta2-agonists were more obvious in neutrophils than in eosinophils. A selective beta2-receptor antagonist, ICI-118551, reversed the inhibitory effect of beta2-agonists (PC, salbutamol, tulobuterol B) on N-formyl methionyl-leucyl-phenylalanine-induced O2- production.

CONCLUSIONS:

These results suggest that beta2-agonists had an inhibitory effect on granulocyte functions, mainly mediated viareceptors and their efficacy. Our observations support that beta2-agonists with a rapid onset of action and high intrinsic efficacy (short-acting and full agonists) may be optimal for the rescue therapy against acute asthma attack and sedation of its airway inflammation in an early phase.

PMID:
16272820
DOI:
10.1159/000089516
[Indexed for MEDLINE]

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