Human beta-interferon incubated with muscle homogenate is protected by albumin but not by proteinase inhibitors.
The scarce bioavailability of beta-interferon (IFN-beta) after intramuscular administration is probably due either to the binding of IFN-beta 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-beta is about 10% of that of recombinant IFN-alpha 2 and then we evaluated the effects of proteinase inhibitors and albumin on IFN-beta incubated at 37 degrees C with muscle homogenate. IFN biological activity decreased spontaneously by about 20% after incubation for 6 hr at 37 degrees C in Hanks' solution, but it was almost completely lost after incubation with muscle homogenate. Proteinase inhibitors (alpha 1-antitrypsin, alpha 2-macroglobulin, aprotinin, soybean trypsin inhibitor, leupeptin, EP-459, and EP-475) failed to block the inactivation of IFN-beta by muscle proteinases, whereas albumin exerted a partial but consistent protection.
Paulesu
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L
Institute of General Physiology, University of Siena, Italy.
Pessina
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GP
Bocci
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D000418:Albumins / Q000494:pharmacology*; D000818:Animals; D001682:Biological Availability; D006801:Humans; D007370:Interferon Type I / Q000097:blood / Q000493:pharmacokinetics; D016899:Interferon-beta / Q000097:blood / Q000378:metabolism / Q000493:pharmacokinetics*; D008297:Male; D009132:Muscles / Q000378:metabolism*; D011480:Protease Inhibitors / Q000494:pharmacology*; D011817:Rabbits; D011994:Recombinant Proteins
D000418:Albumins; D007370:Interferon Type I; D011480:Protease Inhibitors; D011994:Recombinant Proteins; D016899:Interferon-beta