The effects of maternal preeclampsia on inflammatory cytokines and clinical outcomes in premature infants (original) (raw)
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Predictive value of inflammatory cytokines in preeclampsia
Preeclampsia (PE) is a multisystem disorder associated with maternal hypertension, placental abnormalities and adverse fetal outcomes. Endothelial dysfunction and immunological imbalance are the proposed etiological factors for the development of PE. The aim of the study was to assess the concentration of cytokines (IL-1β,IL-6,IL-8 and TNF-α) with progression of normal pregnancy and development of PE.40 primigravidas with uncomplicated normal pregnancies in first trimester which were followed till the last trimester (control) and 35 primigravidas who developed PE (study group) in the third trimester were selected by random sampling. A demographic characteristic along with assessment of cytokines was determined in normotensive and preeclamptic pregnant females. The levels of TNF-α, IL-6 and IL-8 are significantly increased (p<0.001) in PE when compared with the levels in normal healthy controls and normal pregnant females in the third trimester. Also, there is a significant progression (p<0.001) in the levels of TNF-α from the first trimester in females who subsequently developed PE. The present data indicates that measurement of TNF-α early in pregnancy can be used to predict the progression of PE.
Association of pro‐ and anti‐inflammatory cytokines in preeclampsia
Journal of Clinical Laboratory Analysis, 2019
IntroductionThe pro‐ and anti‐inflammatory cytokines play crucial role in the development and functions of placenta. Any changes in these cytokines may be associated with many pregnancy‐related disorders like preeclampsia. Therefore, the present study is aimed to study the expression of pro‐inflammatory (TNF‐α, IL‐6) and anti‐inflammatory (IL‐4, IL‐10) cytokines in placenta and serum of preeclamptic pregnant women.Material and MethodsFor this study, a total of 194 cases of preeclamptic and control cases were enrolled in two Groups as per the gestational age that is, Group I (28‐36 weeks) and II (37 weeks onwards). The number of samples was 55 in Group I and 139 in Group II. The immunohistochemistry (IHC) and enzyme‐linked immunosorbent assay (ELISA) were conducted on placenta and serum of both preeclamptic and normal samples, respectively. IHC results were revalidated by reverse transcriptase PCR (RT‐PCR).ResultsBoth Groups (I, II) of preeclampsia showed amended levels of pro‐ and a...
Revista Brasileira de Ginecologia e Obstetrícia / RBGO Gynecology and Obstetrics, 2021
Objective Preeclampsia (PE) is a pregnancy-specific syndrome characterized by abnormal levels of cytokines and angiogenic factors, playing a role in the disease development. The present study evaluated whether immunological markers are associated with the gestational age and with the disease severity in preeclamptic women. Methods Ninety-five women who developed PE were stratified for gestational age as preterm PE (< 37 weeks) and term PE (≥ 37 weeks of gestation) and compared for disease severity as well as plasma concentration of angiogenic factors and cytokines. The concentrations of placental growth factor (PlGF), vascular endothelial growth factor (VEGF), Fms-like soluble tyrosine kinase (sFlt-1) and soluble endoglin (sEng), as well as the cytokines, tumor necrosis factor-α (TNF-α) and interleukin 10 (IL-10), were determined by enzyme-linked immunosorbent assay (ELISA). Results The comparison between preeclamptic groups showed a higher percentage of severe cases in preterm P...
Evaluation of maternal systemic inflammatory response in preeclampsia
Taiwanese Journal of Obstetrics and Gynecology, 2015
Objective: To evaluate the systemic inflammatory response in preeclampsia compared to normal pregnancy. Materials and methods: The following serum parameters were determined in three groups of patients: leukocytes, neutrophils, tumor necrosis factor-a (TNF-a), interleukin-6 (IL-6), C-reactive protein (CRP), and certain markers of oxidative stress. Fetal status was assessed based on the gestational age at which birth occurred, on the Apgar score, and on fetal weight. Results: In preeclampsia, a higher systemic inflammatory status was found compared to normal pregnancy. Gestational age at birth, fetal weight, and Apgar score were significantly lower in the group with preeclampsia compared to normal pregnancy. Conclusion: In preeclampsia, there is an increased systemic inflammatory response compared to normal pregnancy, which can influence fetal status at birth.
Preterm delivery can be precipitated by infection, and preterm infants are at heightened risk of postnatal infection. Little is known about the ontogeny of inflammatory biomarkers in extremely preterm infants. We hypothesized that suspected prenatal infection (chorioamnionitis or spontaneous preterm labor) and clinically diagnosed postnatal infection would be associated with unique biomarker signatures, and those patterns would be influenced by the degree of prematurity. Venous blood was collected daily for the first week and weekly for up to 14 additional weeks from 142 neonates born at 22-32 weeks gestation. A custom array was utilized to measure monocyte chemoattractant protein-1 (MCP-1) and interleukin-6 (IL-6). C-reactive protein (CRP) levels were obtained from the electronic medical record. 90 infants had suspected prenatal infection and 63 were diagnosed with postnatal infection. Independent of gestational age at delivery, MCP-1 was significantly increased (P < 0.001) in a...
Modulation of pro- and anti-inflammatory cytokine production in very preterm infants
Cytokine, 2003
Background: In premature infants, outcome of infection-associated complications is heterogeneous despite advances in antibiotic treatment and diagnosis. Information on the immune response in preterm infants is limited. Immune modulatory strategies require detailed analysis of mediators and their kinetics. Objective: To determine the kinetics of IL-1b, TNFa, IL-6, IL-8, IL-10, cINF and G-CSF in preterm and term infants in an ex vivo cord blood culture (CBC) endotoxin model. Design and methods: Cord blood of 25 infants was obtained immediately after birth from the fetal side of the placenta and incubated in culture medium (RPMI 1640) in the presence or absence of 500 pg/ml lipopolysaccharide (LPS) for 48 h. TNFa, IL-1b, IL-6 and IL-8 were measured by sequential immunometric assay (IMMULITE Ò , DPC Biermann, Germany); IL-10 (Milenia Biotec, Bad Nauheim, Germany), cINF (Diaclone, Besancon, France) and G-CSF (R & D Systems, Wiesbaden, Germany) were determined by ELISA in supernatants at 0, 4, 8, 12, 24 and 48 h. Infants were stratified into three gestational age groups (32 weeks, 33-36 weeks, !37 weeks). Variations between the groups were first analyzed for significance by Kruskal-Wallis test and pairs were compared by Mann-Whitney-U test. Effects of gestational age, leucocyte count, hematocrit and frequency of antenatal steroid exposure were tested by linear regression analysis. To correct a possible impact of variable, WBC count, cytokine levels were adjusted according to individual leucocyte numbers. Results: LPS-stimulated maximum levels of IL-6, IL-1b,TNFa and G-CSF in CBC were significantly lower in very preterm infants compared to more advanced gestational age groups. After adjusting the cytokine levels for 10 5 leucocytes, a significant effect of gestational age on IL-6 and G-CSF production ðp , 0:05Þ was detected. A non-significant trend towards reduced cytokine levels was observed following multiple antenatal steroid exposures. IL-10 : TNFa ratio increased in very preterm neonates when compared with the advanced gestational age, although the increase was not significant. Conclusions: Pro-inflammatory cytokine activity in CBC correlates with gestational age, whereas IL-10 does not. Although ex vivo synthesis of IL-1b, TNFa, IL-6, G-CSF in CBC depends in part on leucocyte numbers, IL-6 and G-CSF synthesis appeared to be related to immaturity. Non-significant effects of multiple antenatal steroid exposure and increased IL-10 : TNFa ratio in preterm neonates, observed in a small sample size, warrant further investigation.
BJOG: An International Journal of Obstetrics and Gynaecology, 2002
Objective To compare indicators of systemic inflammatory response in the second trimester in women who developed pre-eclampsia with normal pregnancies. Design Prospective nested case control study derived from a cohort of 2190 pregnant women. Blood samples were obtained at 18 weeks of gestation. The following inflammatory parameters were measured: tumour necrosis factor-a (TNF-a), plasminogen activator inhibitor-1 (PAI-1), interleukin-1h (IL-1h), IL-6, IL-10, microCRP and tissue factor (TF). Setting Sample The cases were 71 women who subsequently developed pre-eclampsia. The controls were 71 healthy, pregnant women matched for age, parity and first trimester body mass index (BMI). Methods Venous blood was drawn from fasting subjects into 5 mL test tubes containing EDTA. Samples were analysed for inflammatory parameters : IL-1-h, IL-6, IL-10, TNF-a, PAI-1, TF (ELISA-technique) and CRP (latex-enhanced immunonephelometric assay), strictly according to the manufacturer's recommendation. Main outcome measures The matched case and control subjects were compared by the paired two-tailed Wilcoxon signed rank test. All P values were two-tailed and P < 0.05 was deemed statistically significant. Results We found no differences in plasma concentrations of PAI-1, IL-1h, IL-6, IL-10, microCRP, TNF-a or TF at 18 weeks of gestation between women who subsequently developed pre-eclampsia and matched control women. Conclusion In contrast to findings from women with overt pre-eclampsia, the present study indicates that there are no indications of intensified systemic inflammatory response at 18 weeks of gestation in women who later develop pre-eclampsia.
IL-10, TNF-α & IFN-γ: Potential early biomarkers for preeclampsia
Cellular Immunology, 2013
The present study was designed to evaluate levels of IL4, IL10, TNF-a & IFN-c at early second trimester and 24 h from delivery to assess potential correlation of cytokine variation with preeclampsia. A total of 176 consecutive healthy, normotensive primigravidas with uncomplicated singleton pregnancies were recruited at 14-18 weeks of gestation. Serum cytokine levels were estimated at recruitment and 24 h from delivery. In present study, 14(7.95%) women developed preeclampsia. Levels of IL-10, TNF-a and IFN-c (Mean ± SE) at recruitment were statistically significantly lower in preeclamptic group (39.21 ± 9.46 pg/mL, 73.57 ± 13.37 pg/mL and 0.70 ± 0.20 pg/mL, respectively) than non-preeclamptic group (86.02 ± 4.55 pg/mL, 601.37 ± 63.54 pg/mL and 1.67 ± 0.08 pg/mL, respectively) (p < 0.05). In preeclamptic group, IL-4 and TNF-a levels (Mean ± SE) were significantly higher 24 h from delivery (5.35 ± 0.95 pg/mL and 381.21 ± 43.28 pg/mL, respectively) than at recruitment (2.39 ± 0.71 pg/mL and 73.57 ± 13.37 pg/mL) (p = 0.019 and 0.0001, respectively) while IL-10 and IFN-c levels decreased after delivery but the change was not statistically significant. Therefore, the levels of IL-10, TNF-a and IFN-c between 14 and 18 weeks of gestation may act as potential early biomarkers in the diagnosis of preeclampsia.
MEDIATORS OF FETAL INFLAMMATION IN EXTREMELY LOW GESTATIONAL AGE NEWBORNS
Cytokine, 2001
To establish levels of mediators of inflammation in cord blood and postnatal serum from extremely low gestational age newborns (ELGANs, c28 weeks), we measured sixteen markers of inflammation by recycling immunoaffinity chromatography in 15 ELGANs who had serum sampled at days 2-5. Median levels of IL-1, IL-6, IL-8, IL-11, IL-13, TNF-, G-CSF, M-CSF, GM-CSF, MIP-1 , and RANTES were considerably higher than published values of these inflammatory mediators from term newborns. In three of eight ELGANS who had serial measurements taken, levels of IL-1, IL-6, IL-8, IL-11, TNF-, G-CSF, and MIP-1 declined from initially very high levels to reach an apparent baseline towards the end of the first postnatal week. In these same three infants, GM-CSF and TGF-1 levels increased continuously during the first week. In the other five ELGANs, no consistent changes were observed. We speculate, that in some ELGANs, a fetal systemic inflammatory response is characterized by an antenatal wave of pro-inflammatory cytokines, followed by a second, postnatal wave of anti-inflammatory cytokines. Large epidemiologic studies are needed to clarify relationships among inflammation markers and their expression in the fetal and neonatal circulation over time. Such studies would also add to our understanding of the possible role of inflammatory mediators in the pathophysiology of the major complications of extreme prematurity.