Effect of T-helper 1 cytokines on secretion of T-helper 2 cytokines by term trophoblast cells in culture

A successful pregnancy has been postulated to be the result of a discrete b alance between T-helper 1 (Th 1) and T-helper 2 (Th2) type cytokines involv ed in growth and development of the conceptus. The aim of the present study was to examine the effect of Th1 cytokines (interleukin-1 beta (IL-1 beta) and tumor necrosis factor-alpha (TNF alpha)) on the release of Th2 cytokin es including IL-6 and IL-10 by trophoblast cells obtained from term placent a. Trophoblast cells isolated by enzymatic disaggregation and Percoll gradi ent fractionation were cultured in supplemented medium alone or with varyin g concentrations of the selected recombinant cytokines. After 48 h of incub ation, samples of the culture supernatant were analyzed for the Th2 cytokin es IL-6 and IL-10 using specific ELISA assays. Both IL-I beta and TNF alpha had no effect on the cell number and viability as determined by MTT assay. IL-1 beta significantly, stimulated trophoblast release of lL-6 in a dose- dependent manner (3.3-, 5.5-, 10.3- and 22.4-fold higher compared to the co ntrol at 10, 50, 100, 500 U IL- 1 beta /ml respectively, p < 0.05). TNF<alp ha> also stimulated release of IL-6 by there cells. However, the stimulatio n at lower concentrations was not very high and a significant (p < 0.05) st imulation was observed only at higher concentrations (1.1-, 1.3-, 2.6- and 5.9-fold higher at 500, 1000, 1500, 2000 U TNF<alpha>/ml respectively). In contrast, neither IL- 1 beta or TNF alpha exerted any significant effect on IL-10 release by term trophoblast cells (p > 0.05). The results of this st udy provide evidence that production of Th2 cytokines might be under the co ntrol of different regulatory pathways.