Serum levels of soluble Fas and Fas ligand in pregnant women who smoke.

Abstract

Cigarette smoking during pregnancy is associated with reduced incidence of preeclampsia. Mechanisms of this association are poorly understood. Cytokines, angiogenic, and anti-angiogenic factors are involved in the pathogenesis of preeclampsia. During normal pregnancy, Fas ligand (FasL) present on trophoblasts induces apoptosis of Fas bearing maternal immune cells. In preeclampsia, trophoblasts show increased apoptosis with reduced expression of FasL. We determined serum levels of cytokines, angiogenic (placental growth factor), anti-angiogenic factors (soluble endoglin, soluble fms-like tyrosine kinase-1), soluble Fas (sFas), and soluble FasL (sFasL) in smoking and non-smoking pregnant women. Using enzyme-linked immunosorbent and multiplex assays, we prospectively analyzed serum levels of angiogenic, anti-angiogenic factors, cytokines, sFas and sFasL in normotensive smoking and non-smoking mothers. Exclusion criteria included maternal hypertension, auto-immune disorders, rupture of membranes, evidence of labor, and drug use. Of 100 women recruited to the study, 51 were in the non-smoking and 49 in the smoking group. Except for lower maternal age in the smoking group, there was no difference in gestation, BMI, gravidity, or ethnicity between the two groups. Levels of angiogenic, anti-angiogenic factors, cytokines, and sFas were similar between the two groups but sFasL levels were significantly higher in smoking group (38pg/ml vs. 16pg/ml, p<.001) and remained significant after controlling for confounders. Our study demonstrates higher sFasL levels in pregnant women who smoke. Higher sFasL may explain the reduced incidence of preeclampsia in pregnant mothers who smoke by inducing apoptosis of immune cells which may otherwise induce trophoblast apoptosis.