A bioassay for serum interferon based on induction of 2'5'-oligoadenylate synthetase activity

We have developed a bioassay for interferons (IFN) based on measuring the amounts of 2',5' oligoadenylate synthetase (2-5AS) induced in cells of the THP-1 monocyte line in response to IFN. The assay can be completed in 20 h, gives reproducible results, and is at least 50 times more sensitive to IFN-alpha than conventional cytopathic effect inhibition antiviral assays. It is, respectively, less and much less sensitive to IFN-beta and IFN-gamma. The presence of preexisting 2-5AS activity in a sample does not influence the results. We have used this assay to measure very low levels (0.1-0.5 IU/ml) of endogenously formed IFN-alpha in serum samples from patients with various diseases and also to measure the residual small amounts of IFN-alpha still present in the serum as late as 48 h after an i.m. injection of 3 million IU, which is appreciably later than in previous methods. Thus, our highly sensitive assay offers considerable advantages, not least in relation to the clinical use of IFN.