Circulating levels of cytokines during pregnancy: thrombopoietin is elevated in miscarriage

Abstract

Objective-To evaluate the hypothesis that cytokine levels are associated with miscarriage risk using serum samples collected prior to report of miscarriage.Design-A nested case-control study.Setting-Biospecimens from the multi-site Collaborative Perinatal Project, University of Florida laboratory assessment of IL-1ra, IL-1β, IL-4, IL-6, IFN-γ, TNF-α, TPO and G-CSF.Patients-were obtained from cases of miscarriage (N=439) matched to controls (N=373) by gestational age (GA) at sample collection. Intervention-None. Main outcome measures-,Miscarriage.Results-Increased risk of miscarriage was associated with elevated TPO (AOR: 1.16, 95% confidence interval (CI):1.00 -1.36) and decreased G-CSF (AOR: 0.78, 95% CI 0.64 -0.95). When analysis was restricted to samples collected more than 35 days prior to miscarriage, the effect of G-CSF was not observed (AOR: 0.96, 95% CI 0.72 -1.28), whereas increased risk related to higher TPO remained.Conclusions-Circulating levels of TPO may be associated with increased risk of miscarriage.

Maternal Serum Granulocyte Colony-Stimulating Factor Levels and Spontaneous Preterm Birth

“…10 Although we do not have fresh and frozen sera from the same women, the similar distribution of G-CSF among these two groups suggests that substantial degradation is unlikely to have occurred. It is particularly unlikely for differential degradation to have occurred, so that the effect on estimates would be a bias toward the null, suggesting that, if anything, our results may be underestimates.…”

“…The utility of these assays for evaluation of serum cytokine levels in samples from the CPP repository has been been described previously. 10,11 Briefly, G-CSF was measured with high test-retest reliability-the intraclass correlation coefficient was 0.99-and G-CSF levels measured in frozen CPP samples selected from the repository for these investigations were similar to those observed in serum samples freshly collected. Because specimens had been collected previously and identifying information was removed, the Office of Human Subjects Research at the NIH and IRB at the University of Florida determined this study as exempt from full IRB review.…”

“…We recently conducted a nested casecontrol study of serum cytokine levels and their association with miscarriage in subjects selected from the CPP cohort. 10,11 Based on a hypothesized relation between G-CSF and preterm birth, we used information about G-CSF levels measured in sera from women with live births among those controls for the current investigation. The inclusion criteria for these women were limited to entry to the CPP at or prior to 18 weeks gestation and availability of a biospecimen in the repository.…”

The female reproduction and senescence nexus

“…17 It is thought that shift in balance from TH1 to TH2 cytokines favors successful pregnancy. 4,17,18 Elevated levels of the TH2 cytokines interleukin 6 (IL6) and IL10 are observed in the first trimester of women with normal pregnancy.…”

“…17 It is thought that shift in balance from TH1 to TH2 cytokines favors successful pregnancy. 4,17,18 Elevated levels of the TH2 cytokines interleukin 6 (IL6) and IL10 are observed in the first trimester of women with normal pregnancy. [19][20][21] IL6 is expressed during the implantation window and may have similar and redundant functions as the leukemia inhibitory factor (LIF) protein, 22,23 a cytokine important in implantation, decidualization, and placental development.…”