This study compared Th1-Th2 cytokine profiles in a subgroup of recurrent aborters who had an abortion with those in a subgroup of recurrent aborters who had a successful pregnancy. Fifty-four women with a history of at least three normal pregnancies, 24 women with a history of recurrent spontaneous abortion (RSA) followed by abortion (RSA-->A) and 39 women with a history of RSA followed by normal pregnancy (RSA-->N) were studied. Blood samples and placentas were obtained at the time of delivery or abortion; peripheral blood mononuclear cells were stimulated separately with phytohaemagglutinin and with autologous placental cells, and the secreted cytokines estimated. Peripheral blood mononuclear cells from the RSA-->N subgroup secreted higher concentrations of Th1-type cytokines as compared with normal pregnant women, indicating a higher Th1 bias in these women. However, women in the RSA-->N subgroup had significantly higher concentrations of Th2 cytokines as compared with women in the RSA-->A subgroup. A comparison of Th1:Th2 cytokine ratios indicated a higher Th2 bias in RSA-->N women as compared with RSA-->A women. We conclude that abortion-prone women who proceed to have successful pregnancy are more Th2-biased than abortion-prone women who abort, and that recurrent aborters who undergo spontaneous abortion have a stronger Th1 bias than aborters who have normal pregnancy.

Objective  To examine the effects of dydrogesterone on the production of Th1 and Th2 cytokines by lymphocytes from women undergoing unexplained recurrent spontaneous miscarriage (RSM).Design  Controlled prospective, clinical study conducted in a maternity hospital and a university‐based immunology laboratory.Setting  Faculty of Medicine, Kuwait University and Kuwait Maternity Hospital.Sample  Thirty women with unexplained RSM.Methods  Peripheral blood mononuclear cells (PBMC) from women with unexplained RSM were isolated from venous blood by density gradient sedimentation and stimulated with phytohaemagglutinin (PHA). Culture supernatants assayed for interferon (IFN)‐γ, tumour necrosis factor (TNF)‐α, interleukin (IL)‐4, IL‐6 and IL‐10 by ELISA. Levels of the progesterone‐induced blocking factor (PIBF) were also measured.Main outcome measures  Cytokine production in the presence and absence of progesterone and dydrogesterone.Results  Dydrogesterone significantly inhibited the production of the Th1 cytokines IFN‐γ (P= 0.0001) and TNF‐α (P= 0.005) and induced an increase in the levels of the Th2 cytokines IL‐4 (P= 0.03) and IL‐6 (P= 0.017) resulting in a substantial shift in the ratio of Th1/Th2 cytokines. The effect of dydrogesterone was blocked by the addition of the progesterone‐receptor antagonist mifepristone, indicating that dydrogesterone was acting via the progesterone receptor. Dydrogesterone induced the production of PIBF.Conclusion  Dydrogesterone inhibits the production of the Th1 cytokines IFN‐γ and TNF‐α from lymphocytes and up‐regulates the production of the Th2 cytokines IL‐4 and IL‐6, inducing a Th1 to Th2 cytokine shift.

Concentrations of the T-helper (Th) 1 cytokines interleukin (IL)-2, tumour necrosis factor (TNF) -alpha, TNF-beta and interferon-gamma, Th2 cytokines IL-4, IL-5, IL-6, IL-10 as well as those of soluble CD30 in sera have been examined during the three trimesters of gestation, at delivery in normal pregnancy, and at the time of spontaneous abortion in women with a history of unexplained recurrent spontaneous abortion (RSA). Significantly higher concentrations of the Th2 cytokines IL-6 and IL-10 were found at normal delivery than in women with RSA, and conversely significantly increased concentrations of the Th1-type cytokine TNF-alpha were found in RSA as compared with successful pregnancy. In abortion-prone women who had a successful pregnancy, significantly higher concentrations of IL-6 and significantly lower concentrations of TNF-alpha were found as compared with abortion-prone women who had another abortion, supporting the notion that Th2- and Th1-bias are associated with successful and unsuccessful pregnancy respectively. Serum CD30 concentrations did not correlate with the outcome of pregnancy. These findings support observations drawn from experiments on the cytokine secretion profiles of peripheral blood mononuclear cells and decidual lymphocytes which suggest that normal pregnancy is Th2-biased and that unexplained RSA is associated with Th1-type reactivity.