AN ANTI-CYTOKINE BIOACTIVITY ASSAY FOR INTERFERON-ALPHA, INTERFERON-BETA AND INTERFERON-OMEGA

Interferons-alpha and -beta (IFN-alpha and -beta) are cytokines that a re widely known to induce potent anti-viral activity, However, it has become increasingly apparent that IFN- and -beta exert a variety of ot her biological effects, including anti-tumour and immunomodulatory act ivities, and are increasingly used clinically to treat a range of mali gnancies, myelodysplasias and autoimmune diseases, e.g. IFN-beta for m ultiple sclerosis. The most widely used bioassays for the TFNs are bas ed on their anti-viral activity, but these do not predict the biologic al activity of the IFNs in anti-tumour and immunomodulatory therapies. Thus, we have developed anti-cytokine-based bioassays that may be mor e reflective of such activity and which have several advantages over e xisting anti-viral bioassays, The anti-cytokine bioassay is based on t he ability of IFN-alpha, -beta and -omega to inhibit granulocyte-macro phage-colony-stimulating factor (GM-CSF) induced proliferation of the erythroleukaemic cell line TF-1. This assay can take only 24 h, is sen sitive to 200 fg (0.04 IU) IFN-alpha or -beta and 100 fg (0.02 IU) IFN -omega and is able to detect down to these levels in serum or plasma s amples, The usefulness of anti-cytokine bioassays for IFN-alpha, -beta and -omega is not restricted to the GM-CSF/TF-1 cell format and other alternatives are available, such as erythropoietin (EPO)/TF-1 cells a nd EPO/UT-7-EPO cells. These assays can be made specific for each of t he IFNs by including neutralising antibodies in the bioassay.