INTERLEUKIN-4 AND TRANSFORMING GROWTH-FACTOR-BETA-1 MODULATE THE PRODUCTION OF INTERLEUKIN-1 RECEPTOR ANTAGONIST AND OF PROSTAGLANDIN E(2), BY DECIDUAL CELLS

OBJECTIVE: Increased production of prostaglandins is associated with parturition. The production of interleukin-1 is increased in preterm labor occurring in the setting of infection. Interleukin-1 receptor antagonist prevents the effects of interleukin-1. Interleukin-4 and transforming growth factor-beta inhibit the production of prostaglandin E(2) by monocytes and amnion cells, respectively. In addition, these cytokines enhance the production of interleukin-1 receptor antagonist by monocytes. We investigated whether the production of prostaglandin E(2) and interleukin-1 receptor antagonist by decidual cells is modulated by interleukin-4 and transforming growth factor-beta 1. STUDY DESIGN: Human decidual cells in monolayer culture were treated for 44 hours with interleukin-4 (1 to 100 ng/ml), transforming growth factor-beta 1 (1 to 10 ng/ml), the combination of these cytokines, or vehicle. Production of prostaglandin E(2) and interleukin-1 receptor antagonist was measured by radioimmunoassay and enzyme-linked immunosorbent assay, respectively. The Wilcoxon signed-rank test was used. RESULTS: Both interleukin-4 and transforming growth factor-beta 1 inhibited prostaglandin E(2) production by decidual cells (p < 0.01). Decidual cells produced interleukin-1 receptor antagonist at a basal rate of 26.4 +/- 6.7 pg/mu g protein per 44 hours (n = 13). Interleukin-4 stimulated the production of interleukin-1 receptor antagonist by decidual cells (p < 0.01). Transforming growth factor-beta 1 potentiated the stimulatory effect of interleukin-4 on decidual cell interleukin-1 receptor antagonist production (p < 0.05). CONCLUSION: By suppressing the production of prostaglandin E(2) and enhancing the production of interleukin-1 receptor antagonist by decidual cells, interleukin-4 and transforming growth factor-beta may have a role in inhibiting preterm labor in the setting of infection.