Inhibition of leukotriene C4 and B4 release by human eosinophils with the new 5-lipoxygenase inhibitor 6-hydroxy-2(4-sulfamoylbenzylamino)-4,5,7-trimethylbenzothiazo le hydrochloride.

Eosinophils generate and release leukotrienes C 4 and B 4 (LTC 4 , LTB 4 ) and platelet activating factor (PAF), all of which have the capacity to cause inflammation and tissue injury in the airways. This study has examined the effects of a new 5-lipoxygenase inhibitor, 6-hydroxy-2-(4-sulfamoylbenzylamino)-4,5,7-trimethylbenzothia zole hydrochloride (CAS 120164-49-0, E6080) on the release of LTC 4 , LTB 4 and PAF by human eosinophils, Eosinophils stimulated by 1 μmol/l calcium ionophore A23187 for 15 min released 37.5 ± 2.2 ng, 2.3 ± 0.3 ng and 4.0 ± 0.3 pmol per 10 6 cells of immunoreactive LTC 4 , LTB 4 and PAF, respectively (mean ± SEM, n = 4). LTC 4 and LTB 4 releases were inhibited dose-dependently by the addition of E6080 to the cell suspension. The IC 50 values were 0.26 μmol/l for LTC 4 and 0.23 μmol/l for LTB 4 . PAF release was not inhibited. These results suggest that E6080 is a potent inhibitor of LTC 4 and LTB 4 release from eosinophils and may provide a protective effect against bronchoconstriction during late-phase asthmatic responses.