Human β-Interferon Incubated with Muscle Homogenate is Protected by Albumin but not by Proteinase Inhibitors

Abstract

Abstract

The scarce bioavailability of β-interferon (IFN-β) after intramuscular administration is probably due either to the binding of IFN-β to interstitial matrix, or to lymphatic absorption and/or to local breakdown by lysosomal proteinases from muscle. In this work, we first showed that after intramuscular injection, the apparent bioavailability of natural human IFN-β is about 10% of that of recombinant IFN-α₂ and then we evaluated the effects of proteinase inhibitors and albumin on IFN-β incubated at 37°C with muscle homogenate. IFN biological activity decreased spontaneously by about 20% after incubation for 6 hr at 37°C in Hanks' solution, but it was almost completely lost after incubation with muscle homogenate. Proteinase inhibitors (α₁-antitrypsin, α₂-macroglobulin, aprotinin, soybean trypsin inhibitor, leupeptin, EP-459, and EP-475) failed to block the inactivation of IFN-β by muscle proteinases, whereas albumin exerted a partial but consistent protection.