LEUKOTRIENE SYNTHESIS INHIBITION AND ANTI-IGE CHALLENGE OF HUMAN LUNGPARENCHYMA

The leukotriene (LT) synthesis inhibitors BAY x1005 and MK-886 were ev aluated in human lung parenchyma challenged with an anti-IgE. The anti -IgE-induced LTE(4) release was time- and dose-dependent. Treatment of the parenchyma with indomethacin (3 mu M) prior to anti-IgE challenge inhibited the 6-keto prostaglandin F-1 alpha (6-keto PGF(1 alpha)) re lease and enhanced (36%) the quantities of LTE(4) detected during IgE- stimulations. BAY x1005 and MK-886 were assessed in the presence of in domethacin (3 mu M) acid the IC50 values for both inhibitors were simi lar (0.13 mu M). BAY x1005 (1 mu M) produced the same percent of inhib ition of anti-IgE-induced LTE(4) release in the presence or absence of indomethacin. BAY x1005 (1 mu M) did not alter the 6-keto PGF(1 alpha ) release during anti-IgE challenge. The results indicate that BAY x10 05 and MK-886 are potent inhibitors of LT synthesis when human lung pa renchyma were stimulated by an anti-IgE.