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.