Marcela Drahosova

Cytokines and adhesion molecules in the course of acute myocardial infarction

The plasma levels of interleukin 1 beta (IL 1beta), interleukin 6 (IL 6), interleukin 8 (IL 8), tumor necrosis factor alpha (TNF-alpha), E-selectin, ICAM 1 and C-reactive protein (CRP) have been studied in 24 patients with acute myocardial infarction in the course of 96 h. The plasma IL 1beta and IL 6 levels were continually elevated during the 96 h study period (the peak of plasma IL 1beta level was 22.2 pg/ml, S.D. 8.6, P < 0.001, normal values of IL 1beta are less than 10 pg/ml, the mean peak plasma concentration of IL 6 was 184.9 pg/ml, S.D. 134.7, vs. normal values of 15.57 pg/ml, S.D. 2.4, P < 0.001). The mean plasma IL 8 level was increased for the duration of the study, the mean plasma IL 8 level was 103.0 pg/ml, S.D. 23.4 (normal value was below 30 pg/l, S.D. 8.0) P < 0.001. The plasma TNF-alpha level was elevated throughout the time of observation without any significant peak. The mean plasma TNF-alpha concentration was 46.8 pg/ml, S.D. 2.13, vs. normal value 4.35 pg/ml, S.D. 1.23, P < 0.001. The plasma E-selectin level reached the mean level of 145.1 ng/ml, S.D. 75.4, vs. normal value 29.1-63.4 ng/ml, P < 0.001 at an interval of 15-42 h after the onset of the symptoms. The plasma ICAM 1 level showed only a slight significant increase during the first 36 h. The plasma CRP concentration increased later than IL 6, and reached a peak at 42 h after the onset of the symptoms (69.2 mg/l, S.D. 29.9, vs. 1.2 mg/l, S.D. 4.7, P < 0.0001). We conclude that cytokines and adhesion molecules can play an important role in the mechanisms of tissue injury in the process of ischemia and reperfusion.

The fetal inflammatory response in subgroups of women with preterm prelabor rupture of the membranes.

Abstract Objective: To evaluate the influence of microbial invasion of the amniotic cavity (MIAC) and histological chorioamnionitis (HCA) on the intensity of the fetal inflammatory response and the occurrence of fetal inflammatory response syndrome (FIRS) in preterm prelabor rupture of membranes (PPROM). Methods: One hundred and forty-nine women with singleton pregnancies complicated by PPROM between the gestational ages 24 + 0 and 36 + 6 weeks were included in the study. Blood samples were obtained by venipuncture from the umbilical cord after the delivery of the newborn. The umbilical cord blood interleukin (IL)-6 levels were evaluated using ELISA kits. The fetal inflammatory response was determined by IL-6 levels, and FIRS was defined as an umbilical cord blood IL-6 >11 pg/mL. Result: IL-6 levels and the occurrence of FIRS were higher in women complicated with both MIAC and HCA (median IL-6 35.5 pg/mL, FIRS in 68%) than in women with HCA alone (median IL-6 5.8 pg/mL, FIRS in 36%), MIAC alone (median IL-6 2.8 pg/mL, FIRS in 17%) or women without MIAC or HCA (median IL-6 4.3 pg/mL, FIRS in 29%). There were no differences in IL-6 levels or rates of FIRS among women with MIAC alone or HCA alone and women without both MIAC and HCA. Conclusion: A higher fetal inflammatory response mediated by umbilical cord blood IL-6 was identified when both MIAC and HCA were detected in pregnancies complicated by PPROM.

Cervical fluid IL-6 and IL-8 levels in pregnancies complicated by preterm prelabor rupture of membranes

Abstract Objective: To determine the cervical fluid interleukin (IL)-6 and IL-8 levels in pregnancies complicated by preterm prelabor rupture of membranes (PPROM) and the association of these interleukins with microbial invasion of the amniotic cavity (MIAC) and histological chorioamnionitis (HCA). Methods: Sixty women with singleton pregnancies were included in this study. Cervical fluid was sampled at the time of admission using Dacron polyester swabs, which were placed into the endocervical canal for 20 s. IL-6 and IL-8 levels were determined by ELISA. The management of PPROM was active management (except for in pregnancies <28 weeks of gestation) and occurs not later than 72 h after the rupture of membranes. Result: The women with MIAC had higher IL-6 and IL-8 levels than did the women without MIAC (IL-6: p = 0.01; IL-8: p = 0.003). There was no difference in IL-6 levels between women with and without HCA (p = 0.37). The women with HCA had higher IL-8 levels only in the crude analysis (p = 0.01) but not after adjustment for gestational age (p = 0.06). The women with both MIAC and HCA had higher levels of IL-6 and IL-8 than did the other women (IL-6: p = 0.003; IL-8: p = 0.001). IL-8 level of 2653 pg/mL was found to be the best cut-off point in the identification of PPROM pregnancies complicated by both MIAC and HCA with a likelihood ratio of 24. Conclusions: The presence of MIAC is the most important factor impacting the local cervical inflammatory response, which is determined by IL-6 and IL-8 levels in the cervical fluid. IL-8 levels seem to be a promising non-invasive marker for the prediction of pregnancies complicated by the presence of both MIAC and HCA.

Amniotic fluid soluble Toll-like receptor 2 in pregnancies complicated by preterm prelabor rupture of membranes

Objective: To determine amniotic fluid soluble Toll-like receptor 2 (sTLR2) levels in PPROM according to the presence of microbial invasion of the amniotic cavity (MIAC), histological chorioamnionitis (HCA), and both these conditions. To test the cutoff level of 222.7 ng/mL, as proposed in our previous study, in order to distinguish women with both MIAC and HCA. Methods: 169 women with a gestational age between 24+0 and 36+6 weeks were included in a prospective cohort study. Amniocenteses were performed, and sTLR2 in the amniotic fluid were determined using ELISA. Results: Women with MIAC had higher sTLR2 levels (median 113.2 ng/mL) than those without MIAC (median 47.1 ng/mL; p < 0.0001). Women with HCA did not have a higher sTLR2 level (median 52.6 ng/mL) compared with women without HCA (median 47.1 ng/mL; p = 0.23). Women with both MIAC and HCA had higher sTLR2 levels (median: 311.3 ng/mL) than other women (17.5 ng/mL; p < 0.0001). The cutoff level 222.7 ng/mL had a sensitivity of 63%, a specificity of 98%, and a likelihood ratio of 40.3 for the prediction of both MIAC and HCA. Conclusions: Amniotic fluid sTLR2 is a promising predictor of both MIAC and HCA with high specificity in PPROM.

Amniotic fluid soluble Toll-like receptor 4 in pregnancies complicated by preterm prelabor rupture of the membranes.

Objective: To determine amniotic fluid soluble Toll-like receptor 4 (sTLR4) levels in women with preterm prelabor rupture of the membranes according to the presence of microbial invasion of the amniotic cavity and histological chorioamnionitis and its relation to neonatal outcome. Methods: One hundred two women with singleton pregnancies with a gestational age between 24 + 0 and 36 + 6 weeks were included in a prospective cohort study. Amniocenteses were performed, and the concentrations of sTLR4 in the amniotic fluid were determined using sandwich enzyme-linked immunosorbent assay technique. Results: Women with the presence of microbial invasion of the amniotic cavity had higher sTLR4 levels [median 54.2 ng/mL, interquartile range (IQR) 10.15–289.9] than those without this condition (median 18.1 ng/mL, IQR 8.1–29.9; p = 0.001). Women with the presence of histological chorioamnionitis had a higher sTLR4 level (median 28.0 ng/mL, IQR 11.15–178.1) compared with women without histological chorioamnionitis (median 13.0 ng/mL, IQR 7.8–28.7; p = 0.003). A mixed linear model was used to adjust for confounders. The difference was found only between women with and without microbial invasion of the amniotic cavity in this model. Conclusions: Microbial invasion of the amniotic cavity was associated with higher amniotic fluid sTLR4 levels independent of confounders.

Vaginal fluid IL-6 and IL-8 levels in pregnancies complicated by preterm prelabor membrane ruptures

Abstract Objective: To determine the vaginal fluid interleukin (IL)-6 and IL-8 concentrations in pregnancies complicated by preterm prelabor rupture of membranes and their correlation to microbial invasion of the amniotic cavity (MIAC) as well as histological chorioamnionitis (HCA). Methods: Sixty-eight women with singleton pregnancies were included in this study. Vaginal fluid was collected at the time of admission. IL-6 and IL-8 concentrations in the vaginal fluid were determined using ELISA. Result: Women with MIAC had higher vaginal fluid IL-6 levels compared to those without MIAC (with MIAC: median 374 pg/mL versus without MIAC: median 174 pg/mL; p = 0.03). IL-8 levels were higher in women with MIAC only in the crude analysis but not after adjustment for gestational age. There was no difference in the IL-6 and IL-8 concentrations between those with and without HCA. Women with both MIAC and HCA had higher IL-6 vaginal fluid levels than those without both MIAC and HCA (with MIAC and HCA: median 466 pg/mL versus without MIAC and HCA: median 178 pg/mL; p = 0.02). IL-8 levels were higher in women with MIAC and HCA only in the crude analysis but not after adjustment for gestational age. Conclusions: Vaginal fluid IL-6 but not IL-8 levels reflect the presence of MIAC and both MIAC and HCA.

Umbilical Cord Blood IL-6 as Predictor of Early-Onset Neonatal Sepsis in Women with Preterm Prelabour Rupture of Membranes

Objective To evaluate umbilical cord interleukin (IL)-6 and funisitis as independent predictors of early-onset neonatal sepsis (EONS) in preterm prelabor rupture of membranes (PPROM). Design Prospective cohort study. Setting Evaluation of umbilical cord IL-6 and funisitis as predictors of early-onset neonatal sepsis in PPROM. Population 176 women with PPROM between 23+0−36+6 weeks of gestation. Methods Umbilical cord IL-6 was assayed by ELISA. Funisitis was defined according to the Salafia classification. Data was adjusted by gestational age at delivery and prenatal administration of corticosteroids and antibiotics. Main Outcome Measures Binary logistic regression was performed to assess the independence of umbilical cord IL-6 and funisitis to predict EONS in women complicated with PPROM. Results The rate of EONS was 7%. Funisitis was present in 18% of women. Umbilical cord IL-6 was significantly higher in women complicated with EONS than without [median (range) 389.5 pg/mL (13.9–734.8) vs 5.2 (0.1–801–4), p<0.001]. Umbilical cord IL-6 was the only independent predictor of early-onset neonatal sepsis (odds ratio 13.6, p = 0.004). Conclusion Umbilical cord IL-6 was the only predictor of early-onset neonatal sepsis in PPROM. Contrary to what is reported, funisitis was not.

Soluble Toll-like receptor 1 family members in the amniotic fluid of women with preterm prelabor rupture of the membranes

Objective: To determine soluble Toll-like receptor (sTLR) 1, sTLR2 and sTLR6 concentrations in amniotic fluid (AF) of women with preterm prelabor rupture of membranes (PPROM) and if there is an association with microbial invasion of the amniotic cavity and histological chorioamnionitis (HCA). Methods: Cross-sectional study was performed. Forty-two women with singleton PPROM pregnancies at a gestational age between 24 + 0 and 36 + 6 weeks were included in the study (twenty-two women with presence of both microbial invasion of the amniotic cavity and HCA, and 20 women without microbial invasion of the amniotic cavity and HCA). Amniocenteses were performed, and the concentrations of sTLRs were determined by sandwich enzyme-linked immunosorbent assays. Results: Women with microbial invasions of the amniotic cavity and HCA (n = 22) had significantly higher median sTLR1, sTLR2 and sTLR6 levels than those without (n = 20). (20.4 ng/mL vs. 0.44 ng/mL; p < 0.0001, 577.6 ng/mL vs. 60.7 ng/mL; p < 0.0001 and 0.44 ng/mL vs. 0.26 ng/mL; p = 0.02, respectively). Conclusions: Women with microbial invasion of the amniotic cavity and HCA had higher AF sTLR1, 2 and 6 levels.

Pentraxin 3 in amniotic fluid as a marker of intra-amniotic inflammation in women with preterm premature rupture of membranes

To determine whether amniotic fluid levels of pentraxin 3 (PTX3) are of value in the prenatal diagnosis of acute histological chorioamnionitis in preterm premature rupture of membranes (PPROM).

Cervical and vaginal fluid soluble Toll-like receptor 2 in pregnancies complicated by preterm prelabor rupture of membranes.

Abstract Objective: To determine the cervical and vaginal fluid soluble Toll-like receptor-2 (sTLR2) levels in pregnancies complicated by preterm prelabor rupture of membranes (PPROM) and their correlation to microbial invasion of the amniotic cavity (MIAC) and/or histological chorioamnionitis (HCA). Methods: Sixty-eight women with singleton pregnancies complicated by PPROM were included in this study. Cervical and vaginal fluid was collected at the time of admission, and levels of sTLR2 in the cervical and vaginal fluid were determined using enzyme-linked immunosorbent assay. Result: Women with MIAC and both MIAC and HCA did not have different cervical and vaginal fluid sTLR2 levels compared to those without MIAC and without both MIAC and HCA. Women with HCA had higher cervical fluid sTLR2 levels in crude analysis (with HCA: median 11.6 pg/mL versus without HCA: median 5.5 pg/mL; p = 0.04) but not after adjustment for gestational age at sampling (p = 0.19). No difference in vaginal fluid sTLR2 levels between women with and without HCA was found. A positive correlation between cervical and vaginal fluid sTLR2 levels was identified (rho = 0.54; p < 0.0001). Conclusions: Cervical and vaginal fluid sTLR2 levels did not reflect the presence of MIAC and/or HCA.