A PROGESTERONE-DEPENDENT IMMUNOMODULATORY PROTEIN ALTERS THE TH1 TH2 BALANCE/

In the presence of progesterone, lymphocytes from pregnant females pro duce an immunomodulatory protein known as progesterone induced blockin g factor (PIBF). We tested the effect of this protein on cytokine prod uction by mitogen-activated lymphocytes. Spleen cells from Balb/c mice were incubated with Con A in the presence or absence of PIBF. Superna tants from the activated cells were collected and the concentrations o f IL-3, IL-4, IL-10 and IFN gamma were determined by ELISA. In superna tants from spleen cells activated in the presence of PIBF the concentr ation of IFN gamma was not substantially different from controls howev er, the same spleen cells produced significantly more IL-10, IL-3 and IL-4 than those cultured without the progesterone-induced protein. Whe n CD4(+) and CD8(+) enriched cell suspensions were used as producers o f the cytokines it was found that both populations reacted with an equ ally increased production of IL-3, IL-4 and IL-10 in the presence of P IBF. Although cytokine-producing Th cells can be identified within the CD4(+) population, the present findings suggest that involvement of C D8(+) cells in altered cytokine production cannot be excluded. These d ata indicate that the PIBF affects the Th1/Th2 balance, and via altere d cytokine ratios it contributes to decreased cell-mediated responses during pregnancy.