Introduction
The mechanisms of normal human parturition are still incompletely understood; however, they include a network of biological pathways, including endocrine and paracrine signaling, with participation of the innate immune response.1–5 The inflammatory response associated to human labor is characterized by the highly compartmentalized secretion of cytokines and chemokines by resident and selectively recruited immune cells that infiltrate the reproductive tissues at the end of gestation and are enriched in the maternal-fetal interface.3,6,7 Initial activation resulting in local secretion of inflammatory mediators under sterile conditions in normal spontaneous human labor is not completely characterized; however, it has been linked to activation of inflammasomes in response to endogenous danger signals/alarmins/damage-associated molecular patterns (DAMPs).9–11
The current generation of biomarkers for risk evaluation of preterm birth (PTB) have limited clinical usefulness,10 and accurate prediction of preterm labor (PTL) is difficult due to the multifactorial etiology of PTB as well as existence of various pathophysiological pathways.11–13 Therefore, a single predictor of PTB may have variable utility in symptomatic women compared to asymptomatic women with or without PTL risk factors. It is surprising that despite the accepted concept of selective inflammation associated with spontaneous onset labor in human, local inflammatory mediators are not routinely used as clinical biomarkers for the diagnosis and prediction of labor. Longitudinal reconstruction of the inflammatory response during normal human labor has many limitations and here, we explore cervicovaginal fluid (CVF) cytokines as a proxy of changes occurring in the intrauterine/choriodecidual compartment during initial stage of human labor. We hypothesize that cervicovaginal inflammatory cytokines can be used as biomarkers to predict inflammatory intrauterine processes associated with the onset of labor.