Interleukin-4 and transforming growth factor-beta 1 modulate the production of interleukin-1 receptor antagonist and of prostaglandin E2 by decidual cells.

Abstract

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 E2 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 E2 and interleukin-1 receptor antagonist by decidual cells is modulated by interleukin-4 and transforming growth factor-beta 1. 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 E2 and interleukin-1 receptor antagonist was measured by radioimmunoassay and enzyme-linked immunosorbent assay, respectively. The Wilcoxon signed-rank test was used. Both interleukin-4 and transforming growth factor-beta 1 inhibited prostaglandin E2 production by decidual cells (p < 0.01). Decidual cells produced interleukin-1 receptor antagonist at a basal rate of 26.4 +/- 6.7 pg/micrograms 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). By suppressing the production of prostaglandin E2 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.