TRANSFORMING GROWTH-FACTOR-BETA OPPOSES THE STIMULATORY EFFECTS OF INTERLEUKIN-1 AND TUMOR-NECROSIS-FACTOR ON AMNION CELL PROSTAGLANDIN-E2 PRODUCTION - IMPLICATION FOR PRETERM LABOR

OBJECTIVE: In preterm labor increased concentrations of interleukin-1 and tumor necrosis factor are present in amniotic fluid. These cytokines may promote labor by stimulating the production of prostaglandins by intrauterine tissues. In many biologic processes, transforming growth factor-beta modifies the actions of cytokines. We studied the effect of transforming growth factor-beta on the cytokine-induced prostaglandin E2 production by amnion cells. STUDY DESIGN: Human amnion cells in monolayer culture were treated with interleukin-1, tumor necrosis factor, or vehicle in the presence or absence of transforming growth factor-beta. The prostaglandin E2 production was measured. RESULTS: Transforming growth factor-beta decreased the interleukin-1- or tumor necrosis factor-induced prostaglandin E2 production by 70% to 80% and the basal prostaglandin E2 synthesis by 27%. The synergistic stimulation of prostaglandin E2 production by the combination of interleukin-1 with tumor necrosis factor was inhibited by 80% in cells treated with transforming growth factor-beta. Transforming growth factor-beta-1, -beta-2, and -beta-1,2 were equipotent. CONCLUSION: Transforming growth factor-beta suppresses the cytokine-induced prostaglandin E2 production by amnion cells and may be an important factor in maintaining pregnancy in the face of labor-promoting cytokines.