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Nedocromil sodium inhibits the A23187‐ and opsonized zymosan‐induced leukotriene formation by human eosinophils but not by human neutrophils
Author(s) -
Bruijnzeel P.L.B.,
Hamelink M.L.,
Kok P.T.M.,
Kreukniet J.
Publication year - 1989
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.1989.tb11862.x
Subject(s) - nedocromil sodium , nedocromil , zymosan , leukotriene , leukotriene b4 , chemistry , pharmacology , leukotriene c4 , in vitro , opsonin , immunology , inflammation , medicine , biochemistry , asthma , respiratory disease , alternative medicine , pathology , lung , placebo
1 Inflammatory cells such as eosinophils and neutrophils are thought to contribute actively to the pathogenesis of asthma by the release of bronchoconstrictor mediators including leukotrienes. Previous studies have revealed the almost exclusive synthesis of leukotriene C 4 (LTC 4 ) by human eosinophils and of leukotriene B 4 (LTB 4 ), 20‐OH‐LTB 4 and the non‐enzymatically formed LTB 4 ‐isomers by neutrophils when stimulated in vitro with the calcium ionophore A23187 or opsonized zymosan (OZ). In this study we have investigated whether nedocromil sodium, a new anti‐asthma drug, was capable of inhibiting A23187‐ and OZ‐induced leukotriene formation by these cells. 2 Nedocromil sodium inhibited A23187‐ and OZ‐induced LTC 4 formation by eosinophils in a concentration‐dependent manner (mean IC 30 for A23187: 5.6 × 10 −5 m ; mean IC 30 for OZ: 6.3 × 10 −5 m ), whereas it did not inhibit A23187‐ and OZ‐induced LTB 4 formation by neutrophils. 3 Extension of the preincubation time of the cells with the drug did not alter the observed inhibitory capacity. The optimal preincubation time was 5 min. 4 The in vitro inhibition of LTC 4 formation by eosinophils by nedocromil sodium may be a valuable property of this drug in the treatment of asthma.