The Effect of PGE2 on Murine Helper-T-Cell Lymphokines

Abstract

Prostaglandin E₂ (PGE₂) has selective effects on the production of murine helper-T-cell lymphokines. PGE₂ inhibits production of the Th1-associated lymphokines IL-2 and IFN-γ, but does not inhibit production of the Th2-associated lymphokines IL-4 and IL-5. This could have been due to differences in the Th1 and Th2 cells themselves or to differences in the cytokines. To discriminate between these models we first examined the effect of PGE₂ on IL-3 production, a lymphokine produced by both Th1 and Th2 cells. IL-3 production was inhibited by PGE₂ in some cells and enhanced in others, indicating that some property of the cell was critical. However, the effect on IL-3 production did not cleanly discriminate between Th1 and Th2 cells. Second, we examined the effect of PGE₂ on lymphokine production from Th0 cells. In some cells, production of IL-2, IL-3, and IL-4 was inhibited by PGE₂. In other cells, IL-2 and IL-3 were inhibited while IL-4 production was enhanced. These data again indicated that it was a property of the T cell, not necessarily the lymphokine itself, that determined the response to PGE₂. In Th1 and Th2 clones, both the mode of primary stimulation (antigen and antigen-presenting cells or calcium ionophore) and the presence of costimulation also were found to affect the response of IL-3 production to PGE₂. Therefore, the effect of PGE₂ on lymphokine production appears to depend upon the intracellular signaling pathways that are activated within a particular T cell.