Aberrant cytokine production by peripheral blood mononuclear cells in recurrent pregnancy loss?

Abstract

Successful pregnancy may depend on a Th2-type cytokine response, whilst, conversely, a poor pregnancy outcome may be associated with an increase in Th1 cytokines and a concomitant decrease in Th2 cytokines. This prospective study was designed to elucidate whether a failure of the cytokine shift pre-dated miscarriage and was therefore likely to be an aetiological factor in recurrent pregnancy loss (RPL). Cytokine production by stimulated peripheral blood mononuclear cells from 46 pregnant women who had previously suffered idiopathic RPL during early pregnancy was compared with 25 gestationally age-matched pregnant controls and 11 non-pregnant women. Production of IFN-gamma was lower in pregnant than in non-pregnant women and even lower in RPL pregnant women (P = 0.0191). IL-10 was increased in pregnant women compared with non-pregnant controls, and further increased in RPL patients (P = 0.026). IL-4 was also increased in women with RPL (P = 0.0001). No differences in IFN-gamma, IL-10 or IL-4 secretion were observed in RPL patients who subsequently miscarried compared with those who successfully completed the pregnancy. RPL women with a successful reproductive outcome had similar concentrations of TNF-alpha to pregnant women, RPL women who subsequently miscarried had significantly lower levels than either pregnant women (P = 0.02) or non-pregnant controls (P = 0.0004). Contrary to our hypothesis, the cytokine shift, which appears to characterize normal pregnancy, was accentuated rather than diminished in RPL pregnant women.