Phagocyte activity in the peripheral blood of pregnant women with systemic lupus erythematosus and in the cord blood of their newborns.

AIM: To detect faults in phagocytosis in peripheral blood cells of pregnant women with systemic lupus erythematosus (SLE) and in cord blood of their newborns. METHODS: Pregnant women fulfilled ≥ 4 American College of Rheumatology criteria for SLE and their newborns were recruited. Pregnant women without SLE and their newborns constituted controls. Phagocytosis and respiratory burst were measured using PHAGOTEST and BURSTTEST kits (Biotechnology GmbH, Germany) on FACSCalibur™ flow cytometer. Expression of CD11b was estimated with antibodies (BD Biosciences, San Jose, CA, USA). Mann-Whitney rank-sum test was used to compare SLE group and controls. RESULTS: Phagocytosis and respiratory burst were estimated in blood of 31 SLE women (29.5 ± 3.3 years) and in cord blood of 26 newborns. Controls were 21 health women (29.8 ± 2.8 years) and their 21 babies. Median reactive oxygen species (ROS) production was reduced in the SLE group versus controls (arbitrary units): women, 2315 versus 3316 (P = 0.034); babies, 1051 versus 1791 (P = 0.041), respectively. Proportion of ROS-producing granulocytes decreased in the SLE group: women, 72.5% versus 94.0% (P = 0.025); babies, 46.8% versus 90.7% (P = 0.008). Proportion of phagocytes which engulfed Escherichia coli and bacteria number per phagocyte also decreased in SLE women. Monocyte activity was suppressed in newborns from the SLE group (RLU): 224 versus 507 (P = 0.022). CD11b expression was reduced in SLE women (RLU): granulocytes, 588 versus 1448.5 (P < 0.001); monocytes, 1017 versus 1619 (P = 0.002). CONCLUSION: Pregnant SLE women have low ingesting capacity of phagocytes. Suppression of phagocytosis in their newborns is mainly due to reduced number of cells producing ROS.

The relationship of seminal transforming growth factor-ß1 and interleukin-18 with reproductive success in women exposed to seminal plasma during IVF/ICSI treatment.

It has been proposed that the transforming growth factor (TGF)-ß1 present in seminal plasma (SP) triggers a female immune response favorable for implantation. We hypothesize that seminal interleukin (IL)-18, a cytokine that can potentially cause implantation failure, interferes with the beneficial effect of TGF-ß1. This study aims to determine whether the levels of seminal TGF-ß1 and IL-18 are associated with reproductive outcomes in patients exposed to SP during in vitro fertilization (IVF) or IVF with intracytoplasmic sperm injection (ICSI). A prospective study, which included 71 couples undergoing IVF/ICSI was carried out. Female patients were exposed to their partners' SP via timed intercourse before the day of ovum pick-up (OPU) and also subjected to intravaginal SP application just after OPU. Quantitative measurements of total TGF-ß1 (active plus latent) as well as IL-18 were determined by FlowCytomix™ technology in the SP to be used for intravaginal applications. Comparison of SP cytokine profiles between pregnant and non-pregnant groups revealed that pregnancy was correlated with a lower concentration of IL-18 (P=0.018) and lower content per ejaculate for both of IL-18 (P=0.0003) and TGF-ß1 (P=0.047). The ratio of TGF-ß1-to-IL-18 concentration was significantly higher in the pregnant than in the non-pregnant group (P=0.026). This study supports the notion that two key cytokines TGF-ß1 and IL-18, both present in SP are associated with reproductive outcomes in female patients exposed to SP during IVF/ICSI treatment.

Interrelationships between Immune and Reproductive Systems in Human.

The possibility for normal reproductive functioning in healthy, fertile women exists due to the presence of unique immunologic barriers, and also due to harmonic functioning of immunoregulatory mechanisms. It is believed that cytokines produced by activated lymphocytes, monocytes and macrophages, such as interleukin-1, interleukin-6, gamma-interferon and others, affect the processes of fertilization, development and implantation of the fertile egg in the uterus, and this may be a reason for habitual miscarriage and infertility. One of the most interesting and insufficiently studied trends of reproduction immunology undoubtedly remains the study of immune relationships between the mother and the fetus. Molecules of the major histocompatibility complex HLA G, E, C, expressed by trophoblast and placenta cells, play an important role in this relationship. Especially promising are studies of the role of the cytokine cascade and regulation of the expression of cytokine genes in the processes of fertilization and implantation of an early embryo, and also mechanisms regulating the invasion of trophoblast into the endometrium, which as a result ensures an adequate level of development of the fetoplacental complex. The study of the participation of the apoptosis process in the mechanisms of intrauterine development of the fetus and hypertrophic changes of the endometrium is interesting. Undoubtedly, further studies of the development of the fetus, the molecular-cellular specificities of different types of fetal tissues and the possibility of cellular transplantation as a new therapeutic technology in the case of habitual miscarriages, different forms of gestosis and intrauterine treatment of the fetus, will seem to be important.