INHIBITION OF IONOPHORE-STIMULATED LEUKOTRIENE B-4 PRODUCTION IN HUMAN-LEUKOCYTES BY MONOHYDROXY FATTY-ACIDS

Leukotriene B4 (LTB4) release by Ca ionophore-stimulated human leukocytes was measured by use of selective solvent partition of reaction mixtures and an agarose microdroplet chemokinesis assay, and the inhibitory effects of 4 monohydroxy fatty acids were determined. 15-Hydroxy-eicosatetraenoic acid (15-HETE) was the most effective inhibitor of LTB4 production with an approximate IC50 [mean inhibitory concentration] value of 6 .mu.M and 99% inhibition at 50 .mu.M, whereas 13-hydroxy-octadecadienoic acid (13-HODD) and 12-HETE were weaker inhibitors with approximate IC50 values of 32 .mu.M and 23 .mu.M, and 59% and 68% inhibition at 50 .mu.M, respectively. 13-HODD and 12-HETE, which are present in large amounts in the lesions of the skin disease psoriasis, may act as endogenous modulators of 5-lipoxyganse activity in skin.