Differential release of interleukin-6 from human gestational tissues in association with labour and in vitro endotoxin treatment

Abstract

In this study, we quantified interleukin-6 (IL-6) concentrations in amniotic fluid at term and preterm labour, and determined the gestational tissue source of IL-6. In addition, aspects of the regulatory mechanisms involved in IL-6 release at the time of term labour and in response to bacterial endotoxin, lipopolysaccharide (LPS), have been established. IL-6 concentrations were 2-fold higher in amniotic fluid collected at term compared with preterm gestation, with an additional 2-fold increase in association with term labour. IL-6 was released from all choriodecidual and placental explants but was detected in only 33% of amniotic explant cultures of tissues obtained before labour onset. In contrast, IL-6 was detected in all amniotic, choriodecidual and placental cultures of tissues obtained after term labour onset and delivery, and the mean IL-6 release was significantly higher than that measured in explant cultures of both amniotic (80-fold increase, P < 0.0001) and choriodecidual (3-fold increase, P < 0.02) but not placental explants taken at the time of elective Caesarean section at term before labour onset. LPS significantly (P < 0.05) increased the release of IL-6 from human choriodecidual and placental explants but not amniotic explants, in a time- and dose-dependent manner. IL-6 is a physiological constituent of amniotic fluid and its production by gestational tissues is differentially regulated by LPS and spontaneous labour onset and delivery.

Spontaneous and LPS-induced secretion of cytokines by villous chorion tissue

“…Some authors consider IL-6 as a labor activity marker, because spontaneous labor activity is associated with increased level of this cytokine in the amniotic fluid [2], cervicovaginal secretion [14], and gestation tissues [5,13]. However, other scientists failed to detect unambiguous relationship between labor activity and IL-6 production [3,7,11].…”

Weakening and Rupture of Human Fetal Membranes – Biochemistry and Biomechanics

“…Relaxins, nuclear factor (NF)-kB and toll-like receptor (TLR)-2 are all part of the inflammatory cascade that result in term/preterm labor or weakening and rupture of FM (Bryant-Greenwood et al, 2009;Millar et al, 1998;Werner et al, 2005;Hoebe et al, 2004). The amniotic fluid in normal uncomplicated pregnancy shows elevated pro-inflammatory cytokines (IL-1, IL-6 and TNF-) with increasing gestation (Opsjln et al, 1993;Romero et al, 1990b;Laham et al, 1994Laham et al, & 1996, which is further increased during labor at term (Opsjln et al, 1993;Romero et al, 1990b;Laham et al, 1994;Cox et al, 1997;Maymon et al, 1999;Gunn et al, 1996;Romero et al, 1990aRomero et al, & 1992a. Infection during pregnancy further elevates the levels of these cytokines in amniotic fluid, FM and decidua .…”

Interleukin-8 Release from Human Gestational Tissue Explants: Effects of Gestation, Labor, and Chorioamnionitis1

“…The labor-associated elevation in IL-8 has been observed in myometrium [17] but not in placenta or decidua [13]. Nevertheless, we recently reported a laborassociated increase in the release of IL-1␣ [23], IL-6 [24], and tumor necrosis factor ␣ (TNF␣) [25] from human gestational tissue explants, and some of these cytokines are known to up-regulate IL-8 [4,26]. The aim of this study was to test the hypothesis that IL-8 release from human gestational tissue explants is increased in association with gestation, labor onset, and chorioamnionitis.…”

“…Amnion, choriodecidual, and placental explant cultures were prepared as previously described [24]. The explants were incubated in RPMI 1640 (100 U/ml penicillin, 100 g/ml streptomycin) at 37ЊC in a humidified atmosphere of carbogen (5% CO 2 , 95% O 2 ).…”