The Interplay of the Interleukin 1 System in Pregnancy and Labor

Abstract

This work assessed the temporal coexpression of interleukin 1 (IL-1) and its inhibitor, IL-1 receptor antagonist (IL-1ra), in the cervicovaginal fluid (CVF) beyond 24 weeks gestation including women in spontaneous term labor. Two cohorts of women were recruited at 24 to 35 weeks' gestation (n ¼ 65) and in late pregnancy (>36 weeks' gestation; n ¼ 88). The CVF was serially collected either every 4 weeks between 24 and 35 weeks' gestation (n ¼ 123 samples) or weekly during late pregnancy (n ¼ 240 samples). The IL-1 and IL-1ra were quantitated by enzyme-linked immunosorbent assay, and the effect of vaginal microflora and unprotected sexual intercourse were also investigated. The IL-1b and IL-1ra remain unaltered between 24 and 35 weeks' gestation. At late pregnancy, IL-1a and b concentrations peak at 4 to 14 days prior to labor onset, while IL-1ra decreases with approaching spontaneous term labor (P < .05, 2-way analysis of variance). The IL-1 and IL-1ra were significantly correlated (P < .001, Pearson r). A combined biomarker model of IL-1a, IL-1b, and IL-1ra can predict term labor with 86% sensitivity and 92% specificity. This study indicates a shifting inflammatory balance in the gestational tissues prior to labor onset.

New biomarkers for the prediction of spontaneous preterm labour in symptomatic pregnant women: a comparison with fetal fibronectin

“…A positive fFN result may be confounded by other factors, including recent sexual intercourse, bleeding, digital vaginal examination and amniotic fluid contamination. Our previous studies have shown that recent unprotected sexual intercourse does not affect the expression of albumin (Liong S, Di Quinzio MKW, Fleming G, Permezel M, Georgiou HM, unpublished data), VDBP, 24 IL-1ra 12 or thioredoxin 11 in the CVF. A comprehensive systematic review of 27 published studies recently assessed the accuracy of fFN for the prediction of spontaneous preterm birth in symptomatic women.…”

“…The inclusion of IL-1ra and thioredoxin was based on our previously published observations relating to human parturition. [10][11][12] A summary of the obstetric characteristics of these 129 women and their respective sample numbers is presented in Supporting Information Table S3. Limited sample availability precluded the measurement of all four biomarkers in some cases.…”

Anakinra use during pregnancy: Report of a case with Familial Mediterranean Fever and infertility

“…This may be an explanation for miscarriages when this drug is used early during pregnancy. Apart from its physiological role in early pregnancy, IL1β may have some deleterious effects in late pregnancy (1). Along with IL1α, it may have play role in preterm labor, and serum levels may predict this (9).…”

“…Interleukin-1 (IL-1), the blockade of which is a very attractive and rational primary treatment modality in various types of periodic fever syndromes as well as in cases of familial Mediterranean fever (FMF) resistant or intolerant to colchicine, is known to play physiological and pathological roles in early and late pregnancy, such as trophoblast motility and preterm labor, respectively (1). Pregnancy data with anti-IL1β agents are scarce.…”

Applying SWATH Mass Spectrometry to Investigate Human Cervicovaginal Fluid During the Menstrual Cycle1

“…Previous studies that utilized mass spectrometry-based approaches have only identified peptides and proteins and not applied quantitative methods. To date, most studies that have attempted to characterize cervicovaginal fluid proteins have used samples obtained from pregnant and or laboring women [12][13][14] or in association with cervical cancer [15]. Such samples would be expected to display very different proteomes that those obtained from non-pregnant women.…”