Jarosław Kalinka

Cytokine imbalance in pregnancy complications and its modulation

The phenomenon of pregnancy can be compromised by a number of complications, such as threatened abortion, recurrent spontaneous miscarriage, preeclampsia, and preterm delivery. Research conducted during the last decade has opened up the possibility that cellular immune effectors may underlie such pregnancy complications. Particularly interesting are the effects of pro-inflammatory and anti-inflammatory cytokines on the conceptus and thus on the success or failure of pregnancy. This review focuses on the association between cytokines and the different complications of pregnancy as well as on the possible pathways of the effector function of cytokines in pregnancy loss. This review also goes on to discuss the redirection of the cytokine profile towards one that is more conducive to pregnancy. Among the most promising agents for the modulation of the Th1/Th2 balance are progestogens such as progesterone and dydrogesterone. Recently published studies lead us to propose that a therapeutic approach worth pursuing would be to assess the individual cytokine profiles of women with pregnancy complications and then to adjust individual therapy using the most effective progestogen.

THE IMPACT OF DYDROGESTERONE SUPPLEMENTATION ON HORMONAL PROFILE AND PROGESTERONE-INDUCED BLOCKING FACTOR CONCENTRATIONS IN WOMEN WITH THREATENED ABORTION

Problem:  The therapeutic value of progestogens in threatened abortion is still under debate. In the presence of sufficient progesterone levels during pregnancy, lymphocytes synthesize a mediator [progesterone‐induced blocking factor (PIBF)] that is anti‐abortive in mice. The aim of this study was to evaluate the effect of dydrogesterone on pregnancy outcome of threatened aborters.

Decreased proinflammatory cytokines in cervicovaginal fluid, as measured in midgestation, are associated with preterm delivery.

The main aim of this study was to investigate the relationship between selected proinflammatory cytokines [interleukin IL‐1 alpha (IL‐1α), IL‐1 beta (IL‐1β), IL‐6 and IL‐8] concentrations in cervicovaginal fluid, as measured in midgestation, and the risk of subsequent preterm delivery.

Correlations of selected vaginal cytokine levels with pregnancy-related traits in women with bacterial vaginosis and mycoplasmas

The aim of this study was to examine correlations between vaginal inflammatory cytokines (IL-1alpha, IL-1beta, IL-6 and IL-8) and pregnancy-related traits (gestational age, birth-weight, BMI, weight gain during pregnancy and vaginal pH). Differences in correlation coefficients were examined among bacterial vaginosis (BV) status and the presence or absence of mycoplasmas. A total of 105 women between the 22nd and 34th week of pregnancy were enrolled in this study. There was a strong negative correlation between IL-1alpha and weight gain during pregnancy (r=-0.877, p<0.001) and a strong positive correlation between IL-6 and BMI (r=0.670, p=0.024) in women with normal vaginal flora and mycoplasmas. These correlations were not present in women who had normal flora and no mycoplasmas. In women with BV and no mycoplasmas, there were significant correlations of gestational age with IL-6 (r=0.727, p=0.027) and IL-8 (r=0.689, p=0.040); however, these correlations were not significant in women with mycoplasmas. Our findings support the conclusion that correlations between inflammatory cytokines and pregnancy-related traits are dependent on context, suggesting that expression is labile. In particular, BMI and gestational age correlation differs depending on BV status and the presence or absence of BV-related mycoplasmas such as Mycoplasma hominis and Ureaplasma urealyticum.

Socioeconomic and environmental risk factors of bacterial vaginosis in early pregnancy

Abstract The main aim of this prospective study was to determine the socioeconomic, demographic and environmental factors that may be associated with the occurrence of bacterial vaginosis at early pregnancy in an indigent population from Central Poland. A group of 196 pregnant women was selected randomly from the patients of 10 district maternity units in the Lodz region, Central Poland. Only singleton pregnancies between 8 and 16 week of gestation were qualified for inclusion in the survey. A standard questionnaire covering medical, socioeconomic, demographic, constitutional and environmental items was administered to every subject and was verified with medical records. Cervico-vaginal swabs were collected from the women under study and tested for bacterial vaginosis (BV) according to Spiegels criteria. Based on the results of Gram stain, BV was diagnosed in 51 women (28,5%), grade I microflora among 66 (36,9%) and grade II among 62 women (34,6%). In the univariate analysis, only single marital status proved to be an important risk factor associated with BV during pregnancy, this was confirmed in the multivariate analysis. Pregnant women who present risk factors for abnormal cervicovaginal microflora should be covered by comprehensive prenatal surveillance, which enables early detection and treatment of this pathology. Research that identifies the causal pathways and mechanisms through which social disadvantage leads to a higher risk of preterm birth may help to reduce current socioeconomic and demographic disparities and improve pregnancy outcome.

IL-1β, IL-6 promoter, TNF-α promoter and IL-1RA gene polymorphisms and the risk of preterm delivery due to preterm premature rupture of membranes in a population of Polish women.

Introduction Our previous study revealed that anti-inflammatory cytokine gene polymorphisms increase the risk of spontaneous preterm delivery (PD) in a population of Polish women. Different genetic background of PD due to preterm premature rupture of membranes (pPROM) than PD without pPROM has been suggested. The aim of this study was to examine the relationship between the maternal carriage of polymorphic alleles of the following genes: interleukin 1β(IL-1β [+3953C>T]), interleukin 6 promoter (IL-6 [−174G>C]), tumour necrosis factor promoter (TNF-α [–308G>A]) and interleukin 1 receptor antagonist (IL-1RN) and the risk of PD caused exclusively by pPROM in a population of Polish women. Material and methods A case-control study. 95 Caucasian women were examined including 32 cases and 63 controls. Case subjects experienced a delivery at less than 36 weeks and 6 days of gestation due exclusively to pPROM while control subjects gave birth at term. Polymorphisms were determined by polymerase chain reaction-restriction fragment length polymorphism analysis (PCR-RFLP). Results No statistically significant relationship between polymorphisms of examined genes and risk of PD due to pPROM in a population of Polish women was found: OR = 0.84 (95% CI: 0.34-2.01) for IL-1β, OR = 0.77 (95% CI: 0.27-2.13) for IL-6, OR = 0.72 (95% CI: 0.26-1.90) for TNF-α and OR = 1.74 (95% CI: 0.66-4.64) for IL-1RN. Conclusions Maternal carriage of polymorphic alleles of IL-1β, IL-6 promoter, TNF-α promoter and IL-1RA seems to have no impact on the risk of PD due to pPROM in the population of Polish women.The genetic contribution and pathomechanism of PD related to pPROM seems to differ from those of spontaneous PD without pPROM.

RCAS1 decidual immunoreactivity and RCAS1 serum level during cesarean section with respect to the progression of labor.

RCAS1 (a receptor‐binding cancer antigen expressed on SiSo cells) is a membrane protein present also in a soluble form that seems to be responsible for the suppression of the cytotoxic immune response during gestation. The present study evaluates the decidual immunoreactivity level of RCAS1 and the serum level of RCAS1 with respect to the progression of labor at the time of cesarean section.

Association Between Maternal and Fetal TLR4 (896A>G, 1196C>T) Gene Polymorphisms and the Risk of Pre-term Birth in the Polish Population

Bacteria activates Toll‐like receptor 4 on immune system cells leading to preterm birth (PTB). The aim of study was to evaluate the impact of maternal and fetal carriage of TLR4 gene polymorphisms on the risk of PTB.

The impact of dydrogesterone supplementation on serum cytokine profile in women with threatened abortion.

Problem  The role of increased Th1 cytokine expression in pregnancy failure has been questioned recently. The therapeutic value of progestogens in threatened abortion (TA) is still debated. The aim of this prospective study was to compare serum cytokine [tumor necrosis factor (TNF)‐α, interleukin (IL)‐12 and IL‐10] concentrations in women with TA to those in women with normal pregnancy and to evaluate the impact of dydrogesterone supplementation in the former group on cytokine concentration.

ORIGINAL ARTICLE: RCAS1 Decidual Immunoreactivity and RCAS1 Serum Level During Cesarean Section with Respect to the Progression of Labor

RCAS1 (a receptor‐binding cancer antigen expressed on SiSo cells) is a membrane protein present also in a soluble form that seems to be responsible for the suppression of the cytotoxic immune response during gestation. The present study evaluates the decidual immunoreactivity level of RCAS1 and the serum level of RCAS1 with respect to the progression of labor at the time of cesarean section.