The effect of coelomic fluid on the production of cytokines by the first trimester human placenta

Abstract

ObjectiveTo investigate the modulatory effects of coelomic fluid (CF) on the production of tumour necrosis factor-alpha (TNFα) and its receptors, TNF-R1 and TNF-R2, interferon gamma (IFNγ) and interleukin (IL)-10 by placental villous explants cultured under physiological oxygen (O2) concentration. Study designIn vitro culture of placental villous explants at atmospheric and physiological (6%) O2 levels at varying concentrations of CF. Main outcome measuresConcentration of TNFα, TNF-R1, TNF-R2, IFNγ and IL-10 in culture medium and villous explant homogenates, measured using flowcytometric bead arrays. ResultsThe median level and interquartile range of cytokines and receptors present in CF were: TNFα 0.9 pg/ml (0.85, 0.95); IFNγ 5.38 pg/ml (4.96, 6.18); IL-10 1.59 pg/ml (1.45, 1.76); TNF-R1 6043.65 pg/ml (5961.39, 6187.35) and TNF-R2 3563.52 pg/ml (3390.26, 3635.19). The PO2 of CF was 48.74 mmHg (SEM 1.59), equivalent to 6% O2.Increasing doses of CF significantly (p < 0.05) increased the levels of TNFα, TNF-R1 and TNF-R2 in the culture medium at both O2 concentrations.TNF-R1 levels measured in placental homogenate increased up to 2-fold at both O2 concentrations, but were significantly lower (1.96 fold; p = 0.03) at 6% O2 compared to 20% O2. ConclusionsThe exocoelomic cavity in humans contains high levels of both soluble TNF-R1 and TNF-R2. The addition of CF to placental tissue explants in culture modulates the placental secretion of TNFα-receptors and TNFα at both physiological and atmospheric O2 tension resulting in a concentration much higher than that found in the CF. This may contribute to the maternal inflammatory response previously reported in normal early pregnancy.