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BJOG. 2005 Aug;112(8):1096-101.

Modulation of cytokine production by dydrogesterone in lymphocytes from women with recurrent miscarriage.

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1
Department of Microbiology, Faculty of Medicine, Kuwait University, Kuwait.

Erratum in

  • BJOG. 2005 Nov;112(11):1585.

Abstract

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)-gamma, tumour necrosis factor (TNF)-alpha, 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-gamma (P= 0.0001) and TNF-alpha (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-gamma and TNF-alpha from lymphocytes and up-regulates the production of the Th2 cytokines IL-4 and IL-6, inducing a Th1 to Th2 cytokine shift.

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