Effect of middle molecules on immunological functions.

The cell-mediated immunodeficiency secondary to renal failure is well established and is largely dependent on toxic or inhibitory serum factors. Our approach was to investigate the effect of so-called middle molecules (MM) on in vitro and in vivo immunological functions. A crude fraction of MM isolated from the serum or urines of uremic patients by chromatography on Sephadex G-25 fine was shown to markedly inhibit the lymphocyte proliferation induced in vitro by various phytomitogens or by allogeneic cells. A marked depression of the graft-versus-host reaction was demonstrated in vivo. When rats were continuously infused with MM, a significant delay of skin allograft rejection was obtained. From these results it is clear that the MM fraction contains a potent inhibitor of several T lymphocyte functions.