Cytokine Patterns in Maternal Serum From First Trimester to Term and Beyond

Jarmund, Anders Hagen; Giskeødegård, Guro F.; Ryssdal, Mariell; Steinkjer, Bjørg; Stokkeland, Live Marie Tobiesen; Madssen, Torfinn Støve; Stafne, Signe Nilssen; Stridsklev, Solhild; Moholdt, Trine; Heimstad, Runa; Vanky, Eszter; Iversen, Ann‐Charlotte

doi:10.3389/fimmu.2021.752660

Cited by 63 publications

(73 citation statements)

References 83 publications

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“…On the contrary, our results showed that the values for expression of commonly reported inflammatory markers like TNF‐α, IL‐1β, IFN‐γ, IL‐6 and IL‐8 were well within the range of the variability reported. IL‐12p70 was an exception, for which we reported higher values (Table 2) as compared to levels from other parts of the world 27–30 and also from longitudinal studies carried out using similar multiplex assays 18,21,24,31 . We also recorded higher concentrations for MIP‐1α, MIP‐1β 32 and IL‐1Ra throughout pregnancy, but lower concentrations of IP‐10 (Table 2).…”

Section: Discussionsupporting

confidence: 54%

“…IL-12p70 was an exception, for which we reported higher values (Table 2) as compared to levels from other parts of the world [27][28][29][30] and also from longitudinal studies carried out using similar multiplex assays. 18,21,24,31 We also recorded higher concentrations for MIP-1α, MIP-1β 32 and IL-1Ra throughout pregnancy, but lower concentrations of IP-10 (Table 2). 18,21,24,[31][32][33] Our concentrations for adhesion molecule ICAM-1 were also on the higher side compared to levels reported in a number of studies.…”

Section: Discussionmentioning

confidence: 74%

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Longitudinal changes in serum immune markers during normal pregnancy in a North‐Indian population

Kaushal,

Ayushi,

Sharma

et al. 2022

American J Rep Immunol

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Problem The objective of this study was to examine levels of cytokines across normal term pregnancy in an Indian population. Additionally we have also explored for possible associations between inflammatory markers and fetal growth parameters. Method of Study A multiplex panel of 24 analytes was used to examine levels of inflammatory markers in maternal serum at three time points during pregnancy and in cord blood from women with no reported comorbidities who delivered a singleton live baby at term (N = 23), enrolled in the GARBH‐Ini pregnancy cohort. Linear mixed models were applied to construct longitudinal cytokine trajectories with gestational age. Pearson correlation was used to calculate intra‐visit correlation between cytokines. Principal component analysis (PCA) was performed to examine cytokine combinations prevalent across pregnancy, and their association with fetal growth parameters was determined by multivariable regression. Results Significant increase in sFLT‐1, Flt3L, PLGF, IL‐4, and IL‐18 and a decrease in VCAM‐1 concentrations was seen across pregnancy. The cytokine concentrations in cord blood differed substantially as compared to maternal levels across gestation. Some cytokines were closely correlated with each other in distinct patterns across pregnancy. Gestational age specific combination of cytokines were seen to be associated with different fetal growth parameters. Conclusions This study for the first time provides reference concentrations for the longitudinal expression of immune markers across pregnancy in an Indian population providing a much needed baseline to compare with pregnancies leading to adverse outcomes. Growth factors showed maximum longitudinal variation with gestational age and strong correlations were identified between various cytokines at all time points across pregnancy.

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Section: Discussionsupporting

confidence: 54%

Section: Discussionmentioning

confidence: 74%

Longitudinal changes in serum immune markers during normal pregnancy in a North‐Indian population

Kaushal,

Ayushi,

Sharma

et al. 2022

American J Rep Immunol

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“…Higher fat mass usually predicts higher levels of inflammatory cytokines [ 34 ]; however, we found that, although the plasma level of anti-inflammatory cytokine IL-10 was reduced, the levels of two other proinflammatory cytokines (KC and TNFα) were also decreased. There was also significant reduction in the levels of proinflammatory cytokines (IL-1β, IL-6 and TNFα) in adipose tissues.…”

Section: Discussioncontrasting

confidence: 52%

“…Earlier it was reported that leptin did not modify spontaneous and oxytocin-induced contractions on either human or rat myometria [ 28 ], although another experiment proved its relaxing effect on the human uterus [ 27 ]. A study proved that leptin has a utero-relaxant effect on spontaneous and oxytocin-induced contractions via nitric oxide (NO) and cyclic guanosine monophosphate (cGMP) pathways in late pregnant mice [ 34 ]. Thus, the oxytocin-induced contraction increasing effect of leptin is unusual and may be a rat-specific phenomenon.…”

Section: Discussionmentioning

confidence: 99%

High Fat High Sucrose Diet Modifies Uterine Contractility and Cervical Resistance in Pregnant Rats: The Roles of Sex Hormones, Adipokines and Cytokines

Gáspár

Hajagos-Tóth

Schaffer

et al. 2022

Life

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Background: In obesity, the adipose tissue becomes a very significant endocrine organ producing different factors called adipokines, such as leptin, adiponectin and kisspeptin; however, no data are available about their actions on uterine contraction in obese pregnant rats. Our aim was to study the impact of obesity on pregnant uterine contraction in a rat model. Methods: Obesity was induced by the consumption of a high fat high sucrose diet (HFHSD) for 9 weeks, including pregnancy. Glucose tolerance, sex hormone, cytokine and adipokine levels were measured. Uterine contractions and cervical resistance, as well as their responses to adipokines, were tested along with the expressions of their uterine receptors. Results: HFHSD increased body weight, and altered glucose tolerance and fat composition. The uterine leptin and kisspeptin pathway affect increased. The levels of proinflammatory cytokines were reduced, while the plasma level of progesterone was increased, resulting in weaker uterine contractions, and improving the uterine relaxing effects of adipokines. HFHSD reduced cervical resistance, but the core effect of adipokines is difficult to determine. Conclusions: Obesity in pregnant rats reduces uterine contractility and cytokine-induced inflammatory processes, and therefore obese pregnant rat methods are partially applicable for modelling human processes.

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“…We could adjust for a wide range of potential confounders, such as maternal BMI and fetal sex, with documented associations with both the maternal immune status and autism ( 8 , 30 , 53 ). However, there is a possibility for residual confounding by unmeasured genetic or environmental factors.…”

Section: Discussionmentioning

confidence: 99%

Maternal Levels of Cytokines in Early Pregnancy and Risk of Autism Spectrum Disorders in Offspring

Brynge

Gardner

Sjöqvist

et al. 2022

Front. Public Health

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Previous studies indicate a role of immune disturbances during early development in the etiology of autism spectrum disorders (ASD). Any potential disturbances during fetal development are best addressed by prospective evaluation of maternal markers of inflammation. Previous studies have investigated maternal cytokines, a group of powerful effectors of the immune system, with inconsistent results. In this study, we aimed to clarify the relationship between maternal cytokines and ASD by evaluating levels of 17 cytokines in first trimester maternal serum samples, from 318 mothers to ASD-cases and 429 mothers to ASD-unaffected controls, nested within the register-based Stockholm Youth Cohort. Overall, we observed no consistent associations between levels of maternal cytokines and ASD. While we observed a number of individual associations, the patterns varied across the diagnostic sub-groups. Levels above the 90th percentile of IL-1β (OR = 2.31, 95% CI 1.16–4.60), IL-7 (OR = 2.28, 95% CI 1.20–4.33), IL-13 (OR = 2.42, 95% CI 1.29–4.55), and MCP-1 (OR = 2.09, 95% CI 1.03–4.24) were associated with increased odds of ASD with co-occurring intellectual disability (ID), whereas GMCSF (OR = 2.06, 95% CI 1.03–4.11) and TNF-α (OR = 2.31, 95% CI 1.18–4.50) were associated with increased odds of ASD with ADHD but none survived correction for multiple comparisons. Also, none of the measured maternal cytokines were associated with ASD without co-occurring ID or ADHD. Implementing a data-driven approach using machine learning (Random Forest's Variable Importance measurement), we found no evidence to suggest that adding these cytokines and other markers of maternal immunity, to register-based maternal factors (e.g., psychiatric history) improves prediction of ASD. In summary, we found no robust evidence of an association between maternal immune markers during early pregnancy and ASD.

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Cytokine Patterns in Maternal Serum From First Trimester to Term and Beyond

Cited by 63 publications

References 83 publications

Longitudinal changes in serum immune markers during normal pregnancy in a North‐Indian population

Longitudinal changes in serum immune markers during normal pregnancy in a North‐Indian population

High Fat High Sucrose Diet Modifies Uterine Contractility and Cervical Resistance in Pregnant Rats: The Roles of Sex Hormones, Adipokines and Cytokines

Maternal Levels of Cytokines in Early Pregnancy and Risk of Autism Spectrum Disorders in Offspring

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