The effect of estradiol, but not progesterone, on the production of cytokines in stimulated whole blood, is concentration-dependent.

OBJECTIVES

The purpose of this study was to determine the effects of estradiol and progesterone on interferon-gamma (IFN-gamma), interleukin (IL)-12, IL-10 and tumor necrosis factor-alpha (TNF-alpha) productions in polyclonal activators (phytohemagglutinin+lipopolysaccharide)-stimulated whole blood cultures.

METHODS

Nineteen healthy males and females volunteered in the study. Blood samples were drawn, diluted, and cultured for 24h with different concentrations of estradiol, progesterone or hydrocortisone and then PHA+LPS was added for another 24 h. The supernatant, then, was harvested and assayed for IL-12 p70, IFN-gamma, IL-10 and TNF-alpha.

RESULTS

At preovulatory concentrations, estradiol enhanced significantly IFN-gamma, IL-12 and IL-10, but not TNF-alpha, production levels and reversed the suppressive effect of hydrocortisone in PHA+LPS stimulated whole blood. While IL-10 levels kept increasing at pregnancy estradiol concentrations, IFN-gamma, IL-12 levels and IFN-gamma/IL-10 ratio decreased significantly. No effect of progesterone on IL-12 p70, IFN-gamma, IL-10 and TNF production levels was observed.

CONCLUSIONS

The present study shows that those pregnancy estradiol concentrations (and higher) enhance the production of IL-10 and reduce IL-12, IFN-gamma levels and IFN-gamma/IL-10 ratio in stimulated whole blood cells. Because of the known IL-10 inhibitory actions on T helper (Th) 1 cells and monocytes/macrophages, these high IL-10 levels keep Th2 cytokines favored during pregnancy and may be useful in shifting Th1-mediated autoimmune diseases towards non-pathogenic Th2 pathway.