DIFFERENTIAL-EFFECTS OF CYCLOOXYGENASE PATHWAY METABOLITES ON CYTOKINE PRODUCTION BY T-LYMPHOCYTES

Cyclo-oxygenase pathway metabolites released in the microenvironment b y activated platelets and endothelial cells are potential local modula tors of the immune response, in the present study, we have investigate d the modulatory role of PGE(2), Iloprost (prostacyclin analogue), U-4 6619 (thromboxane analogue) on the release of IL-2, IFN-gamma, TNF-alp ha and IL-6 by T lymphocytes. Our results show that PGE(2) and prostac yclin differ in the regulation of cytokine production. PGE, inhibited the release of IL-2 and IFN-gamma, while Iloprost did not affect their production. The addition of PGE, or Iloprost greatly decreased the am ount of TNF-alpha measured in the supernatants, although the rates of inhibition differed according to the kind of stimulation. Unlike that of PGE(2), inhibition by Iloprost was stronger in alloactivated cultur es than in PHA-stimulated ones. In vitro IL-6 production was stimulate d by PGE(2) in alloactivated cultures and by Iloprost, whatever the st imulus. These results are probably due to other cellular subsets conta minating the T-lymphocyte preparations. After complete removal of mono cytes from cell cultures, there were inhibitory effects of Iloprost an d PGE(2) on IL-6 released in the supernatants. We did not observe any significant effect of thromboxane analogue on the production of either cytokine.