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

Raj Raghupathy, Esraa Al Mutawa, Ma'asoumah Makhseed, Fawaz Azizieh, J. Szekeres-Barthó

Research output: Contribution to journalArticle

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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)-γ, tumour necrosis factor (TNF)-γ, 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.

Original languageEnglish
Pages (from-to)1096-1101
Number of pages6
JournalBJOG: An International Journal of Obstetrics and Gynaecology
Volume112
Issue number8
DOIs
Publication statusPublished - Aug 2005

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Dydrogesterone
Habitual Abortion
Lymphocytes
Cytokines
Interleukin-4
Interferons
Kuwait
Progesterone
Maternity Hospitals
Interleukin-6
Tumor Necrosis Factor-alpha
Progesterone Receptors
Mifepristone
Phytohemagglutinins
Allergy and Immunology
Interleukin-10
Blood Cells
Up-Regulation
Enzyme-Linked Immunosorbent Assay
Medicine

ASJC Scopus subject areas

  • Obstetrics and Gynaecology

Cite this

Modulation of cytokine production by dydrogesterone in lymphocytes from women with recurrent miscarriage. / Raghupathy, Raj; Al Mutawa, Esraa; Makhseed, Ma'asoumah; Azizieh, Fawaz; Szekeres-Barthó, J.

In: BJOG: An International Journal of Obstetrics and Gynaecology, Vol. 112, No. 8, 08.2005, p. 1096-1101.

Research output: Contribution to journalArticle

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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)-γ, tumour necrosis factor (TNF)-γ, 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.",
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