title: Double-blind randomized phase I study on the clinical tolerance and biological effects of natural and recombinant interferon-beta.
abstract: The clinical tolerance of and the effects recombinant human interferon-beta (rHuIFN-beta) obtained from mammalian cells (Chinese hamster ovary cells) exerts on 2',5'-oligoadenyl (2-5A) synthetase activity, human-Mx protein, neopterin, beta 2-microglobulin, interleukin-1 (IL-1) alpha and beta synthesis were compared to those of natural IFN-beta in 12 healthy volunteers. Each subject received a single i.m. injection of 6 x 10(6) IU rHuIFN-beta and natural IFN-beta according to a randomized double-blind cross-over study design. Both were well tolerated and provoked similar changes in clinical indices. Moreover, rHuIFN-beta and natural IFN-beta induced significant and similar increases in 2'-5' adenylates, human Mx protein, and neopterin levels, but neither modulated beta 2-microglobulin, IL-1 alpha or beta synthesis. The sum of these findings indicates that rHuIFN-beta and natural IFN-beta are biologically equivalent. In view of these results, we are of the opinion that these two types of IFN are probably also therapeutically equivalent and, in consequence, that trials to evaluate the response of viral and neoplastic disease patients to rHuIFN-beta are fully justified.
authors.affiliation: Istituto di Clinica Medica I, Università di Perugia, Italy.
authors.forename: A M
authors.initials: AM
authors.lastname: Liberati
authors.forename: M A
authors.initials: MA
authors.lastname: Horisberger
authors.forename: L
authors.initials: L
authors.lastname: Palmisano
authors.forename: S
authors.initials: S
authors.lastname: Astolfi
authors.forename: A
authors.initials: A
authors.lastname: Nastari
authors.forename: S
authors.initials: S
authors.lastname: Mechati
authors.forename: A
authors.initials: A
authors.lastname: Villa
authors.forename: S
authors.initials: S
authors.lastname: Mancini
authors.forename: S
authors.initials: S
authors.lastname: Arzano
authors.forename: F
authors.initials: F
authors.lastname: Grignani
mesh_terms: D015088:2',5'-Oligoadenylate Synthetase / Q000096:biosynthesis / Q000187:drug effects; D000328:Adult; D001708:Biopterins / Q000031:analogs & derivatives / Q000097:blood; D004311:Double-Blind Method; D004790:Enzyme Induction / Q000187:drug effects; D019204:GTP-Binding Proteins; D006403:Hematologic Tests; D006801:Humans; D015151:Immunoblotting; D007273:Injections, Intramuscular; D007370:Interferon Type I / Q000009:adverse effects / Q000494:pharmacology*; D016899:Interferon-beta / Q000009:adverse effects / Q000494:pharmacology*; D007375:Interleukin-1 / Q000097:blood; D008297:Male; D064547:Myxovirus Resistance Proteins; D019798:Neopterin; D014176:Protein Biosynthesis; D011506:Proteins / Q000187:drug effects; D011994:Recombinant Proteins; D012016:Reference Values; D016482:Urinalysis; D001613:beta 2-Microglobulin / Q000187:drug effects
chemical_list: D007370:Interferon Type I; D007375:Interleukin-1; D064547:Myxovirus Resistance Proteins; D011506:Proteins; D011994:Recombinant Proteins; D001613:beta 2-Microglobulin; D001708:Biopterins; D019798:Neopterin; D016899:Interferon-beta; D015088:2',5'-Oligoadenylate Synthetase; D019204:GTP-Binding Proteins