Y-24180, an antagonist of platelet-activating factor, suppresses interleukin 5 production in cultured murine Th-2 cells and human peripheral blood mononuclear cells

Interleukin (IL)-5 has been shown to play an essential role in the pathogen esis of airway inflammation. We investigated the effect of 4-(2-chloropheny l)-2-[2-(4-isobutylphenyl)ethyl]-6, 9-dimethyl-6H-thieno[3,2-f] [1,2,4]tria zolo[3,3-a][1,4]diazepine (Y-24180), an antagonist of platelet-activating f actor (PAF), on the production of IL-5 in cultured D10.G4.1 cells, a murine Th2 clone, and human peripheral blood mononuclear cells (PBMC).;ls a resul t, Y-24180,vas found to suppress both the mRNA expression of IL-5 and the s ubsequent secretion of this cytokine in antigen-stimulated D10.G4.1 cells, Y-24180 also suppressed the production of IL-4, another Th2 type cytokine, at the level of mRNA expression, however, it hardly affected the mRNA. expr ession for IL-6 or IL-10, thus indicating it to have a selective action aga inst IL-5 and IL-4. The suppressive effect of Y-24180 on the secretion of I L-5 by human PBMC was more potent than that of WEB2086, which is another PA F-antagonist. These results suggest that Y-24180 suppresses IL-5 production through a common pathway which also affects the production of IL-4, even t hough the mechanism remains to be elucidated as to whether the PAF-antagoni stic actions are involved or not. (C) 2000 Academic Press.