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.
Pearson
H J
HJ
Department of Haematology, The Royal Infirmary of Edinburgh, Edinburgh.
Stirling
D
D
Ludlam
C A
CA
Steel
C M
CM
D000818:Animals; D001779:Blood Coagulation Factors / Q000276:immunology*; D002455:Cell Division; D002478:Cells, Cultured; D006801:Humans; D007108:Immune Tolerance / Q000276:immunology*; D008214:Lymphocytes / Q000166:cytology; D051379:Mice; D016212:Transforming Growth Factor beta / Q000276:immunology*
D001779:Blood Coagulation Factors; D016212:Transforming Growth Factor beta