IDENTIFICATION OF TRANSFORMING GROWTH-FACTOR-BETA AS A CONTAMINANT INFACTOR-VIII CONCENTRATES - A POSSIBLE LINK WITH IMMUNOSUPPRESSIVE EFFECTS IN HEMOPHILIACS

In previous studies, we have shown that some, but not all low-, interm ediate-, and high-purity factor VIII concentrates inhibit interleukin- 2 (IL-2) secretion from phytohemagglutinin (PHA)-stimulated T lymphocy tes. We now present evidence that this inhibitory action of concentrat es is, at least in part, due to contamination with transforming growth factor-beta (TGF-beta). Originally identified in platelets, TGF-beta is a 25-kD homodimer that has been shown to be a natural and potent in hibitor of many immunologic responses. Using a specific bioassay, we h ave measured IGF-beta in various factor VIII concentrates. While some concentrates contained substantial amounts of the cytokine, there was a wide variation in concentrations of TGF-beta in different products. These levels correlated with the degree of inhibition of IL-2 secretio n from T cells exhibited by each product (P =.0001). Noninhibitory con centrates contained no detectable TGF-beta. Addition of a specific TGF -beta 1 antibody reversed the inhibitory effect of some concentrates o n IL-2 secretion by PHA-stimulated Jurkat T cells and interleukin-5 (I L-5)-induced proliferation of an erythroleukemic cell line. These find ings suggest that TGF-beta contamination is a major contributory facto r to the inhibitory activity of some factor VIII concentrates on cytok ine secretion or activity, and may partially explain the reported immu nosuppressive effects in recipients of these blood products. (C) 1994 by The American Society of Hematology.