Distinct pathophysiologic pathways induced by in vitro infection and cigarette smoke in normal human fetal membranes.

Objective: The purpose of this study was to document distinct pathways that are initiated by lipopolysaccharide and cigarette smoke stimulation of normal term fetal membranes.

Study Design: Fetal membranes from nonsmoking women at term, not in labor, from cesarean deliveries were placed in an organ explant system and stimulated with cigarette smoke extracts (CSEs), lipopolysaccharide, or lipopolysaccharide + CSE. Media were assayed for an interleukin (IL)-1beta, -1 receptor antagonist, -6, -8, -10, tumor necrosis factor alpha, soluble tumor necrosis factor receptors 1 and 2, and matrix metalloproteinases 1, 2, 3, 8, 9, and 12. Tissue homogenates were assayed for apoptotic markers (p53, caspase 3 activity, and cleaved poly [ADP-ribose] polymerase-1).

Results: Lipopolysaccharide stimulation resulted in higher cytokine and matrix metalloproteinase concentrations, whereas it was lower after CSE and CSE + lipopolysaccharide stimulations, compared with control specimens. Apoptotic factors were several folds higher after CSE or CSE + lipopolysaccharide stimulation, compared with control specimens or lipopolysaccharide stimulations.

Conclusion: Cigarette smoke showed immunoinhibitory properties that potentially were mediated by apoptosis and lipopolysaccharide-induced proinflammatory response. This study demonstrated 2 independent pathophysiologic pathways that may alter pregnancy outcome.