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Cytokines are involved in regulating HIV-1 infection. They are also placental environment major components. We assessed the potential impact of HIV-1 infection and/or anti-retroviral drugs on the placental cytokine profiles that may be involved in controlling HIV-1 placental dissemination. Placental explants were obtained after elective caesarean section from anti-retroviral-treated HIV-1-infected pregnant women and from HIV-1 non-infected pregnant women. The main placental cytokines were assessed for protein secretion in the supernatants of 24-h placental culture explants and/or in uncultured placental explants for mRNA expression levels. The cytokine profiles were different between the HIV-1-infected and the non-infected groups. Higher medians of leukaemia inhibiting factor (LIF), tumour necrosis factor (TNF)-α and interleukin (IL)-8 secretion were found in the 24-h culture supernatant of term placenta from HIV-1-infected women. High median levels of IL-16 and regulated upon activation normal T cell expressed and secreted (RANTES) levels were found in both groups. The mRNA expression medians were lower for TNF-α and IL-8 and higher for stromal cell-derived factor-1 (SDF-1) in uncultured placental explants from HIV-1-infected women. In the HIV-1-infected group, but not in the non-infected group, the secretion levels of TNF-α and IL-8, as well as their mRNA expression levels, were highly positively correlated; furthermore, their secretion levels were correlated positively with LIF and IL-10 secretion levels. We found no correlation between the cytokine levels and the immunovirological status of the HIV-1-infected mothers or the type or duration of treatment. These results highlight the potential impact of HIV-1 and of the anti-retroviral treatments on the placental cytokines pattern, independently of their anti-viral activity. [ABSTRACT FROM AUTHOR]

Background: There is strong evidence that locally secreted cytokines control the implantation process and can cause implantation failure. Uterine flushing fluids were analysed to determine their concentrations of leukaemia inhibitory factor (LIF) and tumour necrosis factor (TNF).Methods and Results: We began by flushing the uterine cavities of 33 infertile patients on day 26 of two consecutive cycles. The concentrations of LIF (by enzyme-linked immunosorbent assay) and TNF (by bioassay) were significantly correlated during these cycles (r = 0.762, P = 0.0001 and r = 0.822, P = 0.001 respectively) and hence reliable. Then, after a reference flushing of 30 infertile patients, we followed the outcome of their first consecutive cycle of ovarian stimulation, which preceded either IVF or intrauterine insemination. A total of 10 patients became pregnant. The median concentration of LIF was 0 pg/ml (range: 0-177) and of TNF was 0 U/ml (range: 0-6.17) among those who became pregnant, and 203 pg/ml (range: 0-1620) and 2.14 U/ml (range: 0-16) respectively among those who did not. The LIF concentration was significantly lower in the pregnant group (P = 0.0013).Conclusion: A low concentration of LIF in the uterine flushing fluid at day 26 was predictive of subsequent implantation. Use of this procedure should increase the number of IVF attempts yielding successful pregnancies and also lead to corrective therapies. [ABSTRACT FROM AUTHOR]

The involvement of some interleukins (ILs) in early and established pregnancy has been convincingly demonstrated, but little is known about the potential role of the more recently discovered ones. However, since many of these have positive or negative regulatory effects on both NK and T cells, it is highly probable that they also have regulatory functions in both implantation and placental development. Therefore, as a first step in tackling this problem, we have investigated whether several recently described pro- (IL-12, IL-15) and anti-inflammatory (IL-11, IL-13) cytokines were expressed at the uteroplacental interface by use of immunohistochemistry at different stages of gestation in mice. Each of these molecules was found at the foetomaternal interface, with specific distributions and patterns of expression depending on both the cytokine itself and the stage of pregnancy. The significance of these data is discussed. [ABSTRACT FROM AUTHOR]

Background: The possibility that a specific cytokine profile could be detected in the ovaries of patients with polycystic ovarian syndrome (PCOS) was investigated.Method: Enzyme-linked immunosorbent assay (ELISA) or bioassays were used to assess the concentrations of leukaemia inhibitory factor (LIF), tumour necrosis factor, interleukin 11, gamma interferon, progesterone and oestradiol in follicular fluids from preovulatory follicles collected after ovarian stimulation from 15 PCOS patients, 15 infertile control patients with regular cycles, and 8 oocyte donors.Results: LIF and progesterone concentrations were significantly lower in the follicular fluid of PCOS patients (LIF median: 265 pg/ml) compared with controls (LIF median: 816 pg/ml); LIF and progesterone follicular fluid concentrations were correlated (r = 0.720, P = 0.0001). The LH/FSH ratio was negatively correlated with LIF concentrations (r = - 0.714, P = 0.0075). Although the PCOS and control patients did not differ significantly in age, ovarian reserve or IVF indication, the implantation rate was significantly lower among the women with PCOS (IR = 9 versus 21%, P = < 0.01).Conclusion: The specific cytokine profile of the PCOS patients is probably related to the lower implantation rate since follicular fluid LIF appears to function as an embryotrophic agent. [ABSTRACT FROM AUTHOR]

In utero transmission of HIV-1 has been demonstrated and may account for around 10–20% of all materno–fetal HIV-1 transmission. The possible routes for such transmission are transannexial or transplacental. In both cases, the microenvironment (cytokines and chemokines) at the placental interface could be an important regulatory factor in viral transmission. We therefore performed explant cultures of placental villi, and isolated purified trophoblasts, from term placentae obtained from HIV-1-seropositive and HIV-1-seronegative women in order to assess and compare the cytokine and chemokine secretion profiles using ELISA and semiquantitative RT-PCR. No major differences could be seen in the secretions of cytokines and chemokines at the level of whole placental tissue in HIV-1-positive and HIV-1-negative women. However, variations were observed in the expression of inflammatory cytokines and chemokines from trophoblastic cells, depending on the status of HIV-1 infection of the mothers but not the babies, all of which remained uninfected. The significance of these data is discussed. [ABSTRACT FROM AUTHOR]

Examines CD4 and major HIV-1 co-receptor expression by trophoblast cells from early placentas. Permissivity to infection by several HIV-1 primary isolates; Results indicating that viral entry in vitro may occur through a mechanism independent of both CD4 and chemokine receptors.

Humoral and cellular immune agents of a maternal reaction were investigated during pregnancy. Fluorescence studies performed on mouse placentae at 14 days detected maternal immunoglobulins of mainly IgG1, but also IgG2 subclasses. These immunoglobulins, after acid elution, can rebind the placenta and the thymocytes of the relevant paternal strain in case of allogeneic pregnancies, demonstrating an antibody activity towards both placenta specific and paternal strain antigens. They can specifically enhance a paternal strain tumour allograft on a maternal strain recipient. Spleen cells from an allogeneically pregnant mother can reduce or promote paternal strain tumour allograft on a maternal strain recipient. The aggressive effect is shown with small doses of transferred cells, whereas large doses promote enhancement. The suppression of the cytotoxic response of the recipient was ascribed to T cells by use of anti-θ plus complement. Thus, both the rejection reaction (immune cytotoxic cells) and the facilitation reaction (enhancing antibodies and suppressor cells) were demonstrated during pregnancy. [ABSTRACT FROM AUTHOR]

Human interleukin for DA cells/leukaemia inhibitory factor (HILDA/LIF) is a cytokine with pleiotropic effects involved in successful murine implantation. We evaluated human uterine HILDA/LIF production by monitoring its in-vitro secretion by endometrial explant cultures obtained from individuals in either normal or pathological conditions. The cytokine secretion was standardized using the day 5:day 1 ratio of HILDA/LIF concentration in supernatants of such cultures, hereby termed HILDA/LIF production index (HLPI). Our results confirmed that HILDA/LIF is secreted by the human endometrium as assessed by secretion at every phase of the cycle in either normal fertile women, or women bearing intrauterine devices. This was also the case for samples obtained from infertile women presenting repeated failures of embryonic implantation or unexplained primary sterility. However, the HLPI were significantly lower in those latter two groups when compared to fertile women. These results suggest an abnormal regulation of HILDA/LIF secretion in such circumstances, and the clinical implication of those data is discussed. [ABSTRACT FROM AUTHOR]

Human interleukin for DA cells/leukaemia inhibitory factor (HILDA/LIF) is a cytokine with pleiotropic effects involved in successful murine implantation. We evaluated human uterine HILDA/LIF production by monitoring its in-vitro secretion by endometrial explant cultures obtained from individuals in either normal or pathological conditions. The cytokine secretion was standardized using the day 5: day 1 ratio of HILDA/LIF concentration in supernatants of such cultures, hereby termed HILDA/LIF production index (HLPI). Our results confirmed that HILDA/LIF is secreted by the human endometrium as assessed by secretion at every phase of the cycle in either normal fertile women, or women bearing intrauterine devices. This was also the case for samples obtained from infertile women presenting repeated failures of embryonic implantation or unexplained primary sterility. However, the HLPI were significantly lower in those latter two groups when compared to fertile women. These results suggest an abnormal regulation of HILDA/LIF secretion in such circumstances, and the clinical implication of those data is discussed. [ABSTRACT FROM PUBLISHER]

Analyzes the hormonal regulation of the production and secretion of leukemia inhibitory factor (LIF) by the human endometrium. LIF production in women without ovarian function and in early menopause women; Treatment with oestradiol and progesterone; Enzyme-linked immunosorbent assay.

The European collaborative study of HIV-infected pregnant women in Europe now indicates a 13% risk of fetal HIV infection (originally thought to be about 30%, and possibly higher in some countries)- Several reports suggest transplacental passage. However, the detailed mechanisms associated with such vertical transmission have not yet been clarified. We have examined the possibility that HIV enters placental tissue from maternal blood via binding to CD4 and Fc receptors (FcR) at the trophoblast level, allowing intraplacental infection. Here we report the detection of several FcR with distinct localization in the placental villus as well as CD4 surface expression on human trophoblast cells. In addition, we show that trophoblastic cells interact specifically with the gp120/gp160 viral envelope protein. By their tissue localization, these receptors could be responsible or the entry of HIV into the fetal placental cells. Furthermore, purified placental cells can be directly infected by HIV in vitro, and the infection is inhibited by soluble CD4. This suggests a crucial role of the CD4 receptor but an additional way of entry cannot be excluded. Such an in vitro model may be suitable for further studies concerning placental HIV transmission and its prevention. [ABSTRACT FROM AUTHOR]

There is little detailed information on the distribution of granulocytes-macrophages and lymphocytes at the pre- and peri-implantation period of the embryo in the uterus. Using two monoclonal antibodies (MAS-099C and MRC-OX41) we found that cells labelled with antibodies specific to either T lymphocytes and thymocytes or granulocytes-macrophages were present in the endometrium and myometrium before ovum implantation. Both types of labelled cells appeared to migrate from the uterine lumen to the deep endometrium, where their number peaked on day 4. At the early implantation period (days 5 to 7), there was a total lack of labelled cells around the conceptus. Specific changes before ovum implantation in the distribution or activation state of T lymphocytes and granulocyte macrophages may favour early embryo acceptance. [ABSTRACT FROM AUTHOR]

Discusses the search of the field of reproductive immunology for mechanisms that could explain how maternal T cells are tolerized, anergized or inactivated. Demonstration of T cell anergy, partial clonal deletion and suppression in pregnancy; Role that cytokines may play in fetal allograft survival; Evidence that the innate immune system is systematically primed during a normal pregnancy.