Interferons (IFN) are biological molecules with antiviral, antiproliferative, and immunomodulatory actions. Plasmapheresis (PP) combined with IFN therapy in 24 multiple sclerosis (MS) patients was associated with a rapid increase in detectable IFN levels. We describe the presence of a detectable factor in the serum of MS patients which decreases the efficacy of IFN therapy in these patients. We call this factor "interferon inhibitor factor" (IIF). Standard IFN assay indicates inhibition of WISH cell protection by IFN owing to the presence of IIF in patient's serum. Similar results were also obtained with human fibroblast and human leukocyte IFNs. The best results were obtained with an IFN mixture; results with 1:20 diluted patient's sera showed elevation of 120% greater than 1:10 dilution. With 1:40 dilution, an elevation of 1,041% was noticed. The IIF from patient sera collected during PP was purified and characterized. Native gel electrophoresis of IIF indicates a single protein band; further analysis on SDS gels indicates two bands at the 200 and 21-kD range. ELISA failed to reveal the presence of any anti-IFN antibodies. This study demonstrates the presence of IIF in MS patients' sera which are removed from the circulation by PP. Removal of IIF from circulation was associated with increased IFN levels and clinical improvement as measured by Kurtzke's disability status scale (KDSS).

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