Maternal Cytokine Profile Research Articles

Distinct cytokine profiles in late pregnancy in Ugandan people with HIV

During pregnancy, multiple immune regulatory mechanisms establish an immune-tolerant environment for the allogeneic fetus, including cellular signals called cytokines that modify immune responses. However, the impact of maternal HIV infection on these responses is incompletely characterized. We analyzed paired maternal and umbilical cord plasma collected during labor from 147 people with HIV taking antiretroviral therapy and 142 HIV-uninfected comparators. Though cytokine concentrations were overall similar between groups, using Partial Least Squares Discriminant Analysis we identified distinct cytokine profiles in each group, driven by higher IL-5 and lower IL-8 and MIP-1α levels in pregnant people with HIV and higher RANTES and E-selectin in HIV-unexposed umbilical cord plasma (P-value < 0.01). Furthermore, maternal RANTES, SDF-α, gro α\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$\\mathrm{\\alpha }$$\\end{document}-KC, IL-6, and IP-10 levels differed significantly by HIV serostatus (P < 0.01). Although global maternal and umbilical cord cytokine profiles differed significantly (P < 0.01), umbilical cord plasma profiles were similar by maternal HIV serostatus. We demonstrate that HIV infection is associated with a distinct maternal plasma cytokine profile which is not transferred across the placenta, indicating a placental role in coordinating local inflammatory response. Furthermore, maternal cytokine profiles in people with HIV suggest an incomplete shift from Th2 to Th1 immune phenotype at the end of pregnancy.

Fetal and maternal inflammatory response in the setting of maternal intrapartum fever with and without clinical and histologic chorioamnionitis

Both infectious and noninfectious causes of maternal fever have been linked to adverse neonatal outcomes including low Apg0ar scores, respiratory distress, hypotonia, and neonatal seizures. Even in the absence of infection, the occurrence of intrapartum fever is a strong risk factor for poor long-term neonatal developmental outcomes, including encephalopathy, cerebral palsy, and neonatal death. The primary objective of this study was to compare intrapartum and postpartum maternal and fetal umbilical cord serum levels of cytokines RANTES, interferon-ɣ, interleukin-1β, interleukin-2, interleukin-4, interleukin-6, interleukin-8, interleukin-10, interleukin-13, and tumor necrosis factor-α among nonfebrile patients, febrile patients without clinical chorioamnionitis, and febrile patient with clinical chorioamnionitis. This study was conducted at the Richmond University Medical Center from May 15, 2020 to July 16, 2019. During this time, we recruited 30 nonfebrile patients at >36 gestational weeks who were in labor and collected umbilical cord and pre- and postdelivery maternal serum samples to evaluate the cytokine levels. Placentas were collected for pathologic review and to evaluate the histopathologic findings. These results were compared with 121 patients who developed a fever of >38°C during labor. The febrile patients were further divided based on the presence or absence of clinical chorioamnionitis. A secondary analysis was performed based on the presence of absence of histologic chorioamnionitis. Statistical analysis was performed using IBM Statistical Package for the Social Sciences version 25.0. For the 3 group comparisons, a P value of <.017 was considered statistically significant after application of a Bonferroni correction. A total of 151 patients were included in the study; 30 were nonfebrile patients, 46 were febrile patients with a diagnosis of clinical chorioamnionitis, and 75 were febrile patients without clinical chorioamnionitis. Compared with nonfebrile patients, umbilical cord serum interferon-ɣ, interleukin-1β, interleukin-6, interleukin-8, RANTES, and tumor necrosis factor-α levels were elevated in the presence of maternal hyperthermia irrespective of the diagnosis of clinical chorioamnionitis. Interleukin-6 umbilical cord levels were more than doubled from 63.60 pg/mL (6.09-1769.03 pg/mL) in febrile patients with no clinical chorioamnionitis to 135.77 pg/mL (1.86-6004.78 pg/mL) in febrile patients with clinical chorioamnionitis, making it the only cytokine that was significantly different between these 2 groups. When comparing the intrapartum maternal serum, we found a significant elevation in the interleukin-10, RANTES, and tumor necrosis factor-α levels in the febrile group irrespective of the presence of clinical chorioamnionitis when compared with the nonfebrile group. In the postpartum maternal blood evaluations, tumor necrosis factor-α was the only cytokine that was significantly higher in febrile patients than in nonfebrile controls. In the setting of intrapartum fever, maternal cytokine profiles were similar irrespective of the diagnosis of clinical chorioamnionitis. Even in the absence of clinical or histologic chorioamnionitis, maternal hyperthermia induced elevations in fetal cytokines.

Maternal obesity and developmental programming of neuropsychiatric disorders: An inflammatory hypothesis

Maternal obesity is associated with the development of a variety of neuropsychiatric disorders; however, the mechanisms behind this association are not fully understood. Comparison between maternal immune activation and maternal obesity reveals similarities in associated impairments and maternal cytokine profile. Here, we present a summary of recent evidence describing how inflammatory processes contribute towards the development of neuropsychiatric disorders in the offspring of obese mothers. This includes discussion on how maternal cytokine levels, fatty acids and placental inflammation may interact with foetal neurodevelopment through changes to microglial behaviour and epigenetic modification. We also propose an exosome-mediated mechanism for the disruption of brain development under maternal obesity and discuss potential intervention strategies.

Effects of Progesterone, Dydrogesterone and Estrogen on the Production of Th1/Th2/Th17 Cytokines by Lymphocytes from Women with Recurrent Spontaneous Miscarriage

Anti-inflammatory Th2 cytokines have been shown to be associated with healthy, successful pregnancy while pro-inflammatory Th1 and Th17 cytokines are associated with pregnancy loss due to recurrent spontaneous miscarriage. This nexus between unexplained recurrent spontaneous miscarriage (uRSM) and maternal inflammatory has led to the possibility of using pregnancy-related hormones to modify the maternal cytokine bias in a manner that is conducive to successful pregnancy. We investigated the ability of progesterone, dydrogesterone and estrogen to modulate cytokine production by peripheral blood lymphocytes from women undergoing uRSM. Peripheral blood mononuclear cells (PBMC) from females with uRSM were stimulated in vitro with phytohemagglutinin (PHA) in the presence and absence of progesterone or dydrogesterone or 17β-estradiol. Culture supernatants were assayed for IFN-α, TNF-γ, IL-2, IL-6, IL-10, IL-13, IL-17A, and IL-23 by ELISA. Progesterone and dydrogesterone significantly down-regulated the secretion of the Th1 cytokines IFN-α and TNF-γ, and the Th17 cytokine IL-17A, and IL-23. Additionally, the secretion of the Th2 cytokine IL-6 was up-regulated. Estrogen, on the other hand, decreased the production of IFN-α and IL-2, increased the production of IL-6 but did not affect IL-17A and IL-23 secretion. Progestogens and estrogen can decrease the production of some Th1/Th17 inflammatory cytokines secreted by lymphocytes from uRSM and upregulate the production of anti-inflammatory cytokines. These data support the notion that progestogens can be used for altering maternal cytokine profiles to manage pregnancy complications.

Maternal Cytokine Profiles during Pregnancy Predict Asthma in Children of Mothers without Asthma.

Little is known about whether maternal immune status during pregnancy influences asthma development in the child. We measured cytokine production in supernatants from mitogen-stimulated peripheral blood immune cells collected during and after pregnancy from the mothers of children enrolled in the Tucson Infant Immune Study, a nonselected birth cohort. Physician-diagnosed active asthma in children through age 9 and a history of asthma in their mothers were assessed through questionnaires. Maternal production of each of the cytokines IL-13, IL-4, IL-5, IFN-γ, IL-10, and IL-17 during pregnancy was unrelated to childhood asthma. However, IFN-γ/IL-13 and IFN-γ/IL-4 ratios during pregnancy were associated with a decreased risk of childhood asthma (n = 381; odds ratio [OR], 0.33; 95% confidence interval [CI], 0.17-0.66; P = 0.002; and n = 368; OR, 0.36; 95% CI, 0.18-0.71; P = 0.003, respectively). The inverse relations of these two ratios with childhood asthma were only evident in mothers without asthma (n = 309; OR, 0.18; 95% CI, 0.08-0.42; P = 0.00007; and n = 299; OR, 0.17; 95% CI, 0.07-0.39; P = 0.00003, respectively) and not in mothers with asthma (n = 72 and 69, respectively; P for interaction by maternal asthma = 0.036 and 0.002, respectively). Paternal cytokine ratios were unrelated to childhood asthma. Maternal cytokine ratios in mothers without asthma were unrelated to the children's skin-test reactivity, total IgE, physician-confirmed allergic rhinitis at age 5, or eczema in infancy. To our knowledge, this study provides the first evidence that cytokine profiles in pregnant mothers without asthma relate to the risk for childhood asthma, but not allergy, and suggests a process of asthma development that begins in utero and is independent of allergy.

Effect of prenatal EPA and DHA on maternal and umbilical cord blood cytokines

BackgroundInvestigators have hypothesized that omega-3 fatty acid supplementation may modulate the immune response. However, available evidence is conflicting. We performed this study to investigate the effect of prenatal eicosapentaenoic acid (EPA)- and docosahexaenoic acid (DHA)-rich fish oil supplementation on maternal and fetal cytokine production.MethodsThis study is a secondary analysis of a randomized controlled trial designed to assess whether prenatal EPA- or DHA-rich fish oil supplementation would prevent perinatal depressive symptoms among women at risk. Enrolled participants received EPA-rich fish oil (1060 mg EPA plus 274 mg DHA), DHA-rich fish oil (900 mg DHA plus 180 mg EPA) or soy oil placebo. Maternal venous blood was collected at enrollment (12–20 weeks gestation) and after supplementation (34–36 weeks gestation). Umbilical cord blood was collected at delivery. We analyzed stored plasma specimens for 16 human cytokines using multiplex immunoassays. Maternal and cord blood cytokine levels were compared among the treatment groups. Associations of serum DHA and EPA with maternal and cord blood cytokines were explored via regression analysis.ResultsWe enrolled 126 women, of whom 118 completed the trial. Prenatal supplementation with EPA-rich fish oil significantly lowered maternal IL6, IL15, and TNFα concentrations. However, supplementation with DHA-rich fish oil had no significant effect on maternal cytokine profiles. Maternal serum DHA fraction was significantly associated with IL1α, and maternal serum DHA and EPA fractions were significantly associated with IL 10 concentrations after supplementation. Compared with placebo, supplementation with EPA- or DHA-rich fish oils had no significant effect on cord blood cytokine concentrations.ConclusionsPrenatal supplementation with EPA-rich fish oil significantly reduced levels of several inflammatory cytokines in maternal plasma, while prenatal DHA-rich fish oil had no significant effect on cytokine concentrations. Supplementation with EPA- and DHA- rich fish oil had no significant effect on umbilical cord blood cytokine concentrations.Trial registrationClinical Trial Registration: registration number NCT00711971 7/7/2008.

Increase in serum Interleukin-10 does not alleviate pro-inflammatory MCP-1 production in obese pregnancies

Maternal cytokine profiles during pregnancy are characterized by significant deviations, varying substantially between gestational time points and tissues. Obesity, in turn, is linked with low-grade inflammation in adipose tissue and increased concentrations of systemic inflammatory mediators. However, the balance of pro- and anti-inflammatory cytokines in obese pregnancy has remained elusive. In view of the demonstrations that the obesity is a global epidemic in the population at reproductive age with a strong intergenerational impact, we investigated the relation of gestational immune adaptations and obesity-induced inflammation. We found a significant decrease in systemic IL-1β and MCP-1 concentration from 1st to 3rd trimester of pregnancy while IL-10 concentration increased, respectively. However, in obese pregnancies this reduction of pro-inflammatory mediators was not detected. This may constitute an additional risk factor in obese pregnancies in which the concentration of MCP-1 is already upregulated compared to normal weight mothers.

Increased maternal cytokine production and congenital heart defects

Congenital heart defects (CHDs) are a major cause of infant mortality. Most CHDs are thought to result from genetic, lifestyle, and environmental factors that include maternal obesity, diabetes, toxicant exposure, and alterations in anti-oxidant capacity. Since these well-documented risk factors are also associated with immune dysregulation, we sought to compare the maternal immune response in mothers carrying a fetus with a CHD with those mothers whose pregnancies were not affected by any birth defect. We conducted a case-control study to examine the maternal cytokine profile using multiplex technology in pregnant mothers (subject mean=26 weeks’ gestation). This investigation revealed that whole blood cultures derived from case mothers produced higher levels of certain cytokines and chemokines compared with cultures from control subjects when activated with mitogen. Cultures from case subjects produced higher levels of IL-10, IL-13, IL-4, IL-5, IL-17, and IL-6, when stimulated with mitogen compared with control subjects. Plasma levels of chemokine MIP-1α were higher in cases compared with controls. In contrast, C-reactive protein levels were not statistically different. These results demonstrate the need to further examine the maternal cytokine signature in CHD-affected pregnancies. This information could pave the way toward maternal immunotherapeutic intervention to prevent CHDs, and novel biomarker discovery to improve pre-natal diagnosis.

Changes in the maternal cytokine profile in pregnancies complicated by fetal growth restriction

Fetal growth restriction (FGR) is an important and poorly understood condition of pregnancy, which results in significant fetal, neonatal and long-term morbidity and mortality. The aetiology of FGR is unknown and is likely to result from sub-optimal placental implantation and feto-maternal immunological interaction. The diagnostic criteria for FGR vary between studies, and the condition often occurs with preeclampsia (PET). We present a review of studies of maternal cytokines in FGR and compare these with studies of Small for Gestational Age and PET pregnancies.

Intralipid therapy for recurrent implantation failure: new hope or false dawn?

Recurrent embryo implantation failure (RIF) is a disorder with potentially devastating physiological and psychological manifestations for those affected. Although its prevalence is not uncommon, many of the mechanisms involved still require elucidation. Both organ-specific and systemic autoimmunity are associated with an increased prevalence of recurrent miscarriage and reproductive failure, rendering the role of the maternal immunological system in fertility a key concept. It is believed by some that central to this theme is the maternal cytokine profile, with particularly T-helper (Th) cells. Immune modulating therapies have therefore been mooted as potential therapeutic strategies. Recent reports of high pregnancy rates achievable in women with RIF have added fuel to the debate regarding the effectiveness of intralipid in modulating the immune system. We would like to assess if there is sufficient current evidence of acceptable quality to permit an assumption that intralipid therapy is an effective treatment for women undergoing repeated assisted reproduction cycles. We have concluded that appropriately controlled, large-scale, confirmatory studies are necessary to prove the efficacy of intralipid before it can be recommended for routine use.

Maternal cytokine profiles during pregnancy - predictors for later allergy or just reading the tea leaves?

Maternal cytokine profiles during pregnancy - predictors for later allergy or just reading the tea leaves?

Prenatal Stress Alters Cytokine Levels in a Manner That May Endanger Human Pregnancy

Recent data suggest that prenatal stress negatively affects pregnancy and infant outcome. Existing studies implicate dysregulation of the immune and endocrine systems in stress-related increases in premature labor and poor birth outcome, but no published studies have directly addressed the relationships among these variables during pregnancy. We sought to test the hypothesis that high levels of psychosocial stress and low levels of social support during pregnancy alter maternal cytokine profiles in a manner that contributes to poor birth outcomes. Psychosocial stress and social support were measured in 24 women with overtly normal pregnancies once during each trimester of pregnancy. Levels of interleukin-10 (IL-10), IL-6, and tumor necrosis factor-alpha (TNF-alpha) were assessed concurrently with stress and support measurements. High social support was associated with low stress scores. Elevated stress scores were positively correlated with higher levels of the proinflammatory cytokines IL-6 and TNF-alpha, and with low levels of the antiinflammatory cytokine IL-10. These findings provide initial support for our hypothesis that stress-related neural immune interactions may contribute to pregnancy complications and poor outcome, but require further study to determine the mechanism and significance of these effects.

Pro-inflammatory Maternal Cytokine Profile in Preterm Delivery

Obstetrical & Gynecological Survey: November 2003 - Volume 58 - Issue 11 - p 700-701 doi: 10.1097/01.OGX.0000093668.78362.90

Pro-inflammatory maternal cytokine profile in preterm delivery.

The objective of this study was to determine the levels of cytokines produced by maternal peripheral blood mononuclear cells (PBMC) upon stimulation with a mitogen, with autologous placental cells and with a trophoblast antigen extract. Peripheral blood mononuclear cells from 54 women with a history of successful pregnancy and 30 women undergoing preterm delivery (PTD) were stimulated with the mitogen and antigens, and the cytokine levels in mitogen-stimulated culture supernatants assessed. Significantly higher levels of the type 1 cytokines, interferon (IFN)-gamma and interleukin (IL)-2, were produced by the PTD group than by the normal pregnancy group, which on the contrary showed significantly greater production of the type 2 cytokines, IL-4, IL-5 and IL-10. A comparison of the ratios of type 2 to type 1 cytokines is indicative of a type 1 cytokine bias in PTD. These data are suggestive of a maternal type 1 cytokine bias in PTD.

13 Evidence for a differential maternal cytokine profile in preterm preeclampsia and term preeclampsia

13 Evidence for a differential maternal cytokine profile in preterm preeclampsia and term preeclampsia