INHIBITION OF LEUKOTRIENE FORMATION AND IL-8 RELEASE BY THE PAF-RECEPTOR ANTAGONIST SM-12502

We analyzed the effect of the PAF receptor antagonist +)-cis-3,5-dimet hyl-2-(3-pyridyl)thiazolidin-4-one hydrochloride (SM-12502) on the rel ease of leukotriene B-4 and IL-8 from human leukocytes. Peripheral blo od from healthy donors was separated in two different fractions: polym orphonuclear leukocytes (PMN) and a lymphocyte, monocyte and basophil granulocyte cell fraction (LMB). After incubation of the cell populati on with different concentrations of SM-12502 the cells were subsequent ly stimulated with either the Ca ionophore A23187, the bacterial deriv ed peptide fMLP, or with an activator of heterotrimetric G-proteins, t he sodium fluoride (NaF, in the presence of Al3+). The PAF receptor an tagonist led to a concentration and time dependent inhibition of LTB(4 ) formation and IL-8 release from PMN and LMB, Our data clearly indica te an inhibitory effect of the PAF receptor antagonist SM-12502 on the formation of mediators of the lipoxygenase pathway and on the release of IL-8.