Interleukin‐7, T helper 1, and regulatory T‐cell activity‐related cytokines are increased during the second trimester of healthy pregnancy compared to non‐pregnant women

Abstract

ProblemHealthy pregnancy is associated with a physiologic increase in inflammatory responses. The objective of this study was to assess changes in plasma cytokines associated with uncomplicated pregnancy.Method of studyTo examine these changes, plasma levels of immune response mediators from healthy gravidas (N = 115, gestation weeks 23‐30) were compared with those from healthy non‐pregnant women (N = 42). Comparisons were performed using multiplex analysis for Th1 activity‐related cytokines (IFN‐γ, IL‐2, sIL‐2Rα, IL‐12[P70], and IL‐27), Th2 activity‐related cytokines (IL‐4, IL‐5, and IL‐13), other immune response mediators (GM‐CSF, IL‐1β, sIL‐1RI, IL‐6, IL‐8, IL‐15, IL‐17A, IL‐17F, IL‐21, IL‐22, IL‐23, TGFβ1, TGFβ2, TGFβ3, and TNFα), regulatory T cell–related cytokines (IL‐10 and sTNFRII), adipokines (adiponectin, leptin, PAI‐1, and resistin), chemokines (IP‐10, MCP‐1, and MIP‐1β), and hematopoietic growth factor IL‐7.ResultsMultivariate linear regression models showed increased levels of IL‐7, Th1‐, and Treg activity‐related cytokines and decreased levels of adipokines and chemokines in healthy gravidas compared with healthy non‐pregnant women. Additionally, season of the year, age, pre‐pregnancy body mass index, and HLA‐DR/DQ genotypes for type 1 diabetes risk showed different and sometimes reciprocal influence on cytokine levels.ConclusionOur study stresses the importance of profiling immune response mediators during pregnancy to better understand the effect of healthy pregnancy on cytokine levels.

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

“…A role for CRP in this context supports the anti-inflammatory state of second trimester ( 1 , 10 ) and warrants caution for using CRP alone to monitor inflammation in pregnancy. IL-7 also peaked in the second trimester and has been suggested important for maintaining fetal tolerance through the induction of δγ T cells and uterine NK cells ( 61 ). Previously, increasing ( 4 ) or stable ( 15 , 62 ) levels of IL-7 have been reported, but then measured at different time points in pregnancy.…”

The immune system and microbiome in pregnancy

“…However, studies investigating serum cytokine levels in healthy pregnancy over the three trimesters have been inconsistent. A recent study showed increased levels of both Treg cytokines (IL-10, sTNFRII) as well as Th1 cytokines (INFg, IL-2, IL-12, IL-27) during the second trimester of pregnancy [51]. Two studies reported a decrease in TNFa from early to late pregnancy [52,53], although three other studies did not corroborate this finding [54e56] and one reported an increase of TNFa across the trimesters [57].…”

Identification of the correlations between interleukin-27 (IL-27) and immune-inflammatory imbalance in preterm birth

“…These findings were in line with our study, as IL-27/IL-27 R expression was detected in peripheral blood, chorion, decidua, myometrium, and placenta of normal pregnancies (Figure 1). Depending upon the conditions, the IL-27/IL-27R exerts either pro-inflammatory or antiinflammatory effects to maintain the immune homeostasis in pregnancy [50][51][52]. Thus, altered levels of IL-27/IL-27R are of great importance in the development of gestational complications.…”