Leukotriene synthesis inhibition and anti-ige challenge of human lung parenchyma

The leukotriene (LT) synthesis inhibitors BAY x1005 and MK-886 were evaluated in human lung parenchyma challenged with an anti-IgE. The anti-IgE-induced LTE4 release was time- and dose-dependent. Treatment of the parenchyma with indomethacin (3 microM) prior to anti-IgE challenge inhibited the 6-keto prostaglandin F1 alpha (6-keto PGF1 alpha) release and enhanced (36%) the quantities of LTE4 detected during IgE-stimulations. BAY x1005 and MK-886 were assessed in the presence of indomethacin (3 microM) and the IC50 values for both inhibitors were similar (0.13 microM). BAY x1005 (1 microM) produced the same percent of inhibition of anti-IgE-induced LTE4 release in the presence or absence of indomethacin. BAY x1005 (1 microM) did not alter the 6-keto PGF1 alpha release during anti-IgE challenge. The results indicate that BAY x1005 and MK-886 are potent inhibitors of LT synthesis when human lung parenchyma were stimulated by an anti-IgE.