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      Low-Grade Metabolically-Induced Inflammation Mediators Interleukin-6, Adiponectin, and TNF-α Serum Levels in Obese Pregnant Patients in the Perinatal Period

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          Abstract

          Background

          Obesity is a major clinical problem. The number of obese pregnant women is rising rapidly. The consequences of obesity are significant and affect every aspect of perinatal care for both the mother and the developing fetus. Adipose tissue may be responsible for chronic subclinical inflammation in obesity, being a source of inflammatory mediators. The study was designed to evaluate the analysis of the serum concentration of inflammatory mediators, including interleukin-6 (IL-6), tumor necrosis factor alpha (TNF-α), and adiponectin, in obese pregnant women at full-term pregnancies.

          Material/Methods

          The study included 40 women with body mass index (BMI) less than 30 and 24 pregnant women with BMI equal to or greater than 30, admitted to the Perinatology and Obstetrics Department of the University Hospital in Cracow in the first stage of labor. Blood samples were taken from patients to detect the serum concentration of cytokines. Ultrasound was used to evaluate the development of the fetus, including estimated fetal weight, Doppler flows, and the amount of amniotic fluid. We also included the history of chronic diseases and other complications of the pregnancy. A p-value <0.05 was considered significant.

          Results

          The level of adiponectin in obese patients as compared to controls was significantly lower. There was no statistically significant difference in either group when TNF-α and IL-6 were measured. The results of the survey are consistent with previous reports.

          Conclusions

          The exact role of inflammation in pregnancy is not well understood. Determining the exact functions of the different cytokines in physiological pregnancy and pregnancy complicated by obesity requires further study.

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          Most cited references29

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          Longitudinal changes in serum proinflammatory markers across pregnancy and postpartum: effects of maternal body mass index.

          The maternal immune system undergoes substantial changes to support healthy pregnancy. Although obesity is a primary driver of inflammation and predictive of perinatal complications, additive effects of pregnancy and obesity on changes in inflammatory processes are not well delineated.
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            Longitudinal assessment of maternal endothelial function and markers of inflammation and placental function throughout pregnancy in lean and obese mothers.

            Obesity in pregnancy is increasing and is a risk factor for metabolic pathology such as preeclampsia. In the nonpregnant, obesity is associated with dyslipidemia, vascular dysfunction, and low-grade chronic inflammation. Our aim was to measure microvascular endothelial function in lean and obese pregnant women at intervals throughout their pregnancies and at 4 months after delivery. Plasma markers of endothelial function, inflammation, and placental function and their association with microvascular function were also assessed. Women in the 1st trimester of pregnancy were recruited, 30 with a body mass index (BMI) less than 30 kg/m(2) and 30 with a BMI more than or equal to 30 kg/m(2) matched for age, parity, and smoking status. In vivo endothelial-dependent and -independent microvascular function was measured using laser Doppler imaging in the 1st, 2nd, and 3rd trimesters of pregnancy and at 4 months postnatal. Plasma markers of endothelial activation [soluble intercellular cell adhesion molecule-1 (sVCAM-1), soluble vascular cell adhesion molecule-1 (sVCAM-1), von Willebrand factor (vWF), and plasminogen activator inhibitor (PAI)-1], inflammation (IL-6, TNFalpha, C-reactive protein, and IL-10), and placental function (PAI-1/PAI-2 ratio) were also assessed at each time point. The pattern of improving endothelial function during pregnancy was the same for lean and obese, but endothelial-dependent vasodilation was significantly lower (P < 0.05) in the obese women at each trimester (51, 41, and 39%, respectively). In the postpartum period, the improvement in endothelial-dependent vasodilation persisted in the lean women but declined to near 1st trimester levels in the obese (lean/obese difference, 115%; P < 0.01). There was a small but significant difference in endothelial-independent vasodilation between the two groups, lean response being greater than obese (P = 0.021), and response declined in both groups in the postpartum period. In multivariate analysis, time of sampling had the most impact on endothelial-independent function [18.5% (adjusted sum of squares expressed as a percentage of total means squared), P < 0.001 for sodium nitroprusside response; 9.8%, P < 0.001 for acetylcholine response], and obesity had the most impact on endothelial-dependent microvascular function (1.7%, P = 0.046 for sodium nitroprusside response; 19.3%, P < 0.001 for acetylcholine response). Time of sampling (11.2%, P < 0.001), IL-6 (4.0%, P = 0.002), and IL-10 (2.4%, P = 0.018) were significant independent contributors to variation in endothelial-dependent microvascular function. When obesity was entered into the model, the association with IL-6 and IL-10 was no longer significant, and obesity explained 6.8% (P < 0.001) of the variability in endothelial-dependent microvascular function. In the 1st trimester, obese women had a significantly higher PAI-1/PAI-2 ratio [obese median (interquartile range), 0.87 (0.54-1.21) vs. lean 0.30 (0.21-0.47), P < 0.001), reflecting the lower PAI-2 levels in obese pregnant women. In a multivariate analysis, 1st trimester BMI (7.6%, P = 0.012), IL-10 (8.2%, P < 0.001), and sVCAM-1 (0.73%, P = 0.007) contributed to the 1st trimester PAI-1/PAI-2 ratio. Obese mothers have a lower endothelium-dependent and -independent vasodilation when compared with lean counterparts. There was a higher PAI-1/ PAI-2 ratio in the 1st trimester in obese women, which improved later in pregnancy. Obese pregnancy is associated with chronic preexisting endothelial activation and impairment of endothelial function secondary to increased production of inflammatory T-helper cells-2 cytokines.
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              Reviews: adipocytokines in normal and complicated pregnancies.

              Human pregnancy is characterized by insulin resistance, traditionally attributed to the effects of placental hormones. Normal pregnancy-induced insulin resistance is further enhanced in pregnancy complications, associated with disturbed placental function, such as gestational diabetes mellitus, preeclampsia, and intrauterine growth restriction. Compelling evidence suggests that these pregnancy disorders are associated with future development of maternal metabolic syndrome. However, the pathogenetic mechanisms underlying the association between abnormal placental development, insulin resistance, and maternal metabolic syndrome are not fully understood. A large body of evidence has recently supported the role of adipose tissue in the regulation of insulin resistance in both nonpregnant and pregnant participants. In this respect, adipocytokines, which are adipocyte-derived hormones, have been implicated in the regulation of maternal metabolism and gestational insulin resistance. Adipocytokines, including leptin, adiponectin, tumor necrosis factor alpha, interleukin 6, as well as the newly discovered resistin, visfatin, and apelin, are also known to be produced within the intrauterine environment. However, data concerning the pattern of adipocytokines secretion in normal and complicated pregnancies are still limited and partially contradictory. Given the importance of adipose tissue and its hormones in terms of adequate metabolic control and energy homeostasis, we present a review of published data related to the role of adipocytokines in pregnancy, especially in relation to pregnancy complications. Focus will be placed on the functions and other potential roles of the novel adipocytokines resistin, visfatin, and apelin.
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                Author and article information

                Journal
                Med Sci Monit Basic Res
                Med Sci Monit Basic Res
                Medical Science Monitor Basic Research
                Medical Science Monitor Basic Research
                International Scientific Literature, Inc.
                2325-4394
                2325-4416
                2017
                12 January 2017
                : 23
                : 1-7
                Affiliations
                [1 ]Clinical Department of Obstetrics and Perinatology, University Hospital, Cracow, Poland
                [2 ]Clinical Department of Gynaecology and Endocrinology, University Hospital, Cracow, Poland
                Author notes
                Corresponding Author: Małgorzata Zembala-Szczerba, e-mail: gosiazem@ 123456hotmail.com
                [A]

                Study Design

                [B]

                Data Collection

                [C]

                Statistical Analysis

                [D]

                Data Interpretation

                [E]

                Manuscript Preparation

                [F]

                Literature Search

                [G]

                Funds Collection

                Article
                902273
                10.12659/MSMBR.902273
                5248566
                28077838
                a357b743-a40f-4848-9482-7ba943d20a9e
                © Med Sci Monit, 2017

                This work is licensed under Creative Common Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0)

                History
                : 07 November 2016
                : 08 November 2016
                Categories
                Human Study

                adiponectin,adipose tissue,interleukin-6,obesity,pregnancy complications,tumor necrosis factor-alpha

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