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

Abstract

Objective: To 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 design: In vitro culture of placental villous explants at atmospheric and physiological (6%) O2 levels at varying concentrations of CF. Main outcome measures: Concentration of TNFα, TNF-R1, TNF-R2, IFNγ and IL-10 in culture medium and villous explant homogenates, measured using flowcytometric bead arrays. Results: The 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. Conclusions: The 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.