Human Reproduction, Vol. 17, No. 9, 2439-2444,
September 2002
© 2002 European Society of Human Reproduction and Embryology
Aberrant cytokine production by peripheral blood mononuclear cells in recurrent pregnancy loss?
1 Department of Immunology, 2 Department of Obstetrics and Gynaecology, University of Liverpool, L69 3BX, UK and 3 Department of Obstetrics and Gynaecology, Niigata University School of Medicine, Japan
BACKGROUND: 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). METHODS: 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. RESULTS: Production of IFN-
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-, 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-
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). CONCLUSIONS: Contrary to our hypothesis, the cytokine shift, which appears to characterize normal pregnancy, was accentuated rather than diminished in RPL pregnant women.
Key words: cytokines/peripheral blood monocytes/pregnancy outcome/recurrent pregnancy loss
4 To whom correspondence should be addressed at Department of Immunology, Duncan Building, Daulby Street, Liverpool L69 3GA, UK. E-mail: g.s.vince{at}liverpool.ac.uk
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