Progesterone-induced blocking factor (PIBF) modulates cytokine production by lymphocytes from women with recurrent miscarriage or preterm delivery.
Spontaneous miscarriage and preterm delivery are common complications of pregnancy. Pro-inflammatory cytokines have been shown to be associated with recurrent spontaneous miscarriage (RSM) and preterm delivery (PTD) and these have led to exploration of ways to downregulate pro-inflammatory cytokines and/or to upregulate anti-inflammatory cytokines. Progesterone-induced blocking factor (PIBF) is a molecule with inhibitory effects on cell-mediated immune reactions. We have ascertained the effects of PIBF on secretion of selected type 1 and type 2 cytokines by peripheral blood mononuclear cells from healthy non-pregnant women, women undergoing normal pregnancy, women with unexplained RSM and women with PTD. Peripheral blood mononuclear cells from 30 women with a history of unexplained RSM, 18 women undergoing PTD, 11 women with normal pregnancy and 13 non-pregnant healthy women were stimulated with a mitogen in the absence and presence of PIBF after which the levels of cytokines released into culture supernatants were determined by ELISA. Production of the type 2 cytokines IL-4, IL-6 and IL-10 by lymphocytes from the RSM and PTD groups and of IL-4 and IL-10 by lymphocytes from healthy pregnant women was significantly increased upon exposure to PIBF, while the levels of type 1 cytokines were not affected. Ratios of type 1:type 2 cytokines were decreased, suggesting a shift towards Th2 bias. PIBF did not affect cytokine production by lymphocytes from non-pregnant women. Thus, PIBF acts on lymphocytes in pregnancy to induce a type 1 to type 2 cytokine shift by upregulating the production of type 2 cytokines.
Department of Microbiology, Faculty of Medicine, Kuwait University, Kuwait. raj@hsc.edu.kw
R
R
Raghupathy
E
E
Al-Mutawa
M
M
Al-Azemi
M
M
Makhseed
F
F
Azizieh
J
J
Szekeres-Bartho
D000026:Abortion, Habitual / Q000097:blood / Q000276:immunology* / Q000473:pathology; D002478:Cells, Cultured; D016207:Cytokines / Q000378:metabolism*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D007108:Immune Tolerance; D008213:Lymphocyte Activation; D010920:Placenta / Q000276:immunology* / Q000473:pathology; D011247:Pregnancy; D011257:Pregnancy Proteins / Q000276:immunology / Q000378:metabolism*; D047928:Premature Birth / Q000097:blood / Q000276:immunology* / Q000473:pathology; D013491:Suppressor Factors, Immunologic / Q000276:immunology / Q000378:metabolism*; D018417:Th1 Cells / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D018418:Th2 Cells / Q000276:immunology / Q000378:metabolism / Q000473:pathology
D016207:Cytokines; C110058:PIBF1 protein, human; D011257:Pregnancy Proteins; D013491:Suppressor Factors, Immunologic