TGF-beta is not the principal immunosuppressive component in coagulation factor concentrates

Coagulation factor concentrates are known to inhibit a variety of immune reactions when assessed in vitro. This study assessed the immunomodulatory activity of a wide range of coagulation factor concentrates by measuring their inhibition of PHA-stimulated lymphocyte proliferation and reduction in IL-2 secretion. The hypothesis that TGF-beta is responsible for most of these effects was tested by measuring biologically active TGF-beta and immunoreactive TGF-beta1 in the concentrates and comparing the levels recorded with immunosuppressive activity. In addition, the coagulation factors were compared directly with a standard preparation of TGF-beta in a TGF-beta-specific bioassay and in lymphocyte proliferation assays. Although there was a broad correlation between levels of total or active TGF-beta and immunosuppressive activity across all of the coagulation factors tested, individual data sets showed clear discrepancies. Implying that TGF-beta probably serves as a surrogate marker for other immunomodulatory contaminants and that neither TGF-beta nor any other single substance could account for all of the immunosuppressive activity observed. Furthermore, there was a difference of more than 100-fold in the relative potencies of coagulation factors and pure TGF-beta, when compared in immunosuppression assays, indicating that the different assays did not measure the same substance. Whereas anti-TGF-beta antibody almost completely blocked the activity of coagulation factor concentrates (TGF-beta-specific bioassay) and abrogated the effect of authentic TGF-beta (immunosuppression assays) at high concentrations it achieved <50% reversal of the immunosuppressive effects of coagulation factors in immunosuppression assays. These findings indicated that TGF-beta accounted for only a minor proportion of the immunosuppressive activity in most coagulation factor concentrates.