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

Coagulation factor concentrates are known to inhibit a variety of immune re actions when assessed in vitro. This study assessed the immunomodulatory ac tivity of a wide range of coagulation factor concentrates by measuring thei r 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 immunorea ctive TGF-beta 1 in the concentrates and comparing the levels recorded with immunosuppressive activity. In addition, the coagulation factors were comp ared directly with a standard preparation of TGF-beta in a TGF-beta-specifi c bioassay and in lymphocyte proliferation assays, Although there was a bro ad correlation between levels of total or active TGF-beta and immunosuppres sive 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 neithe r TGF-beta nor any other single substance could account for all of the immu nosuppressive activity observed. Furthermore, there was a difference of mor e than 100-fold in the relative potencies of coagulation factors and pure T GF-beta, when compared in immunosuppression assays, indicating that the dif ferent assays did not measure the same substance. Whereas anti-TGF-beta ant ibody almost completely blocked the activity of coagulation factor concentr ates (TGF-beta-specific bioassay) and abrogated the effect of authentic TGF -beta (immunosuppression assays) at high concentrations it achieved <50% re versal of the immunosuppressive effects of coagulation factors in immunosup pression assays. These Endings indicated that TGF-beta accounted for only a minor proportion of the immunosuppressive activity in most coagulation fac tor concentrates.