Nedocromil sodium inhibits the A23187- and opsonized zymosan-induced leukotriene formation by human eosinophils but not by human neutrophils.
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 C4 (LTC4) by human eosinophils and of leukotriene B4 (LTB4), 20-OH-LTB4 and the non-enzymatically formed LTB4-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 LTC4 formation by eosinophils in a concentration-dependent manner (mean IC30 for A23187: 5.6 X 10(-5) M; mean IC30 for OZ: 6.3 X 10(-5) M), whereas it did not inhibit A23187- and OZ-induced LTB4 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 LTC4 formation by eosinophils by nedocromil sodium may be a valuable property of this drug in the treatment of asthma.
Bruijnzeel
P L
PL
Department of Pulmonary Disease, State University Hospital Utrecht, The Netherlands.
Hamelink
M L
ML
Kok
P T
PT
Kreukniet
J
J
D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D001249:Asthma / Q000097:blood; D000001:Calcimycin / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D004804:Eosinophils / Q000187:drug effects / Q000378:metabolism*; D006801:Humans; D006967:Hypersensitivity / Q000097:blood; D066298:In Vitro Techniques; D007975:Leukotriene B4 / Q000096:biosynthesis*; D017835:Nedocromil; D009504:Neutrophils / Q000187:drug effects / Q000378:metabolism*; D015363:Quinolones / Q000494:pharmacology*; D015054:Zymosan / Q000037:antagonists & inhibitors* / Q000494:pharmacology
D000894:Anti-Inflammatory Agents, Non-Steroidal; D015363:Quinolones; D017835:Nedocromil; D007975:Leukotriene B4; D000001:Calcimycin; D015054:Zymosan