A progesterone-dependent immunomodulatory protein alters the Th1/Th2 balance

In the presence of progesterone, lymphocytes from pregnant females produce an immunomodulatory protein known as progesterone induced blocking factor (PIBF). We tested the effect of this protein on cytokine production by mitogen-activated lymphocytes. Spleen cells from Balb/c mice were incubated with Con A in the presence or absence of PIBF. Supernatants from the activated cells were collected and the concentrations of IL-3, IL-4, IL-10 and IFN gamma were determined by ELISA. In supernatants from spleen cells activated in the presence of PIBF the concentration of IFN gamma was not substantially different from controls however, the same spleen cells produced significantly more IL-10, IL-3 and IL-4 than those cultured without the progesterone-induced protein. When CD4+ and CD8+ enriched cell suspensions were used as producers of the cytokines it was found that both populations reacted with an equally increased production of IL-3, IL-4 and IL-10 in the presence of PIBF. Although cytokine-producing Th cells can be identified within the CD4+ population, the present findings suggest that involvement of CD8+ cells in altered cytokine production cannot be excluded. These data indicate that the PIBF affects the Th1/Th2 balance, and via altered cytokine ratios it contributes to decreased cell-mediated responses during pregnancy.