Abnormal TGFbeta levels in the amniotic fluid of Down syndrome pregnancies.

The status of cytokines in amniotic fluid (AF) from chromosomally abnormal pregnancy is largely undefined. TGFbeta plays a key role in fetal growth and differentiation and is responsible for the immunoregulatory activity of AF in normal pregnancy, but its status in Down syndrome (DS) pregnancies is unknown. In addition we investigated the IL-2 status of AF from DS pregnancies. Midtrimester AF from chromosomally normal (n = 25) and abnormal pregnancies with DS (n = 15) were assayed for bioactive and latent TGFbeta levels using the mink lung epithelial cell growth inhibition bioassay and for IL-2 activity by the CTLL-2 cell proliferation bioassay and by ELISA. Levels of bioactive TGFbeta (mean 4.6+/-0.6 U/mL) were significantly increased in DS AF compared with the normal samples (mean 2.8+/-0.3 U/mL, P<0.003) but latent TGFbeta levels did not differ between DS and normal groups. In addition DS AFs showed reduced IL-2 like bioactivity compared with normal samples (P = 0.0006) but IL-2 immunoactivity was undetectable in DS and normal AFs by ELISA. DS AFs display increased TGFbeta activity and lacked IL-2 immunoactivity. The reduced ability of DS AFs to stimulate CTLL-2 cell proliferation is unrelated to the IL-2 status of AF. Altered TGFbeta levels may prove useful as an additional biochemical index for the detection of DS pregnancies.