title: A direct comparison of biological response modulation and clinical side effects by interferon-beta ser, interferon-gamma, or the combination of interferons beta ser and gamma in humans.
abstract: To directly compare clinical side effects and biological response modification, IFN-beta ser, IFN-gamma, or the combination of IFN-beta ser plus IFN-gamma was administered to 21 cancer patients. Each IFN or the combination was given intravenously on days 1, 8, and 15 in varied order. Each IFN and the combination resulted in significant (P less than 0.05) modulation of IFN-induced proteins. IFN-beta ser was more effective than IFN-gamma in enhancing 2-5A synthetase activity (P = 0.001). IFN-gamma was more effective than IFN-beta ser in enhancing serum beta 2 microglobulin expression (P = 0.05) and indoleamine dioxygenase activity, as assessed by decreased serum tryptophan (P = 0.03). The combination enhanced tryptophan catabolism more effectively than IFN-beta ser in a dose-dependent manner (P less than 0.03). IFN-beta ser/IFN-gamma did not potentiate natural killer cells or antibody-dependent cellular toxicity (ADCC). IFN-beta ser/IFN-gamma enhanced monocyte guanylate cyclase activity, as assessed by serum neopterin, more effectively than IFN-gamma alone (P = 0.005). Both IFNs and the combination resulted in increases in HLA class II expression on monocytes. However, no significant difference in the level of induction of HLA DQ and HLA DR expression between IFN-beta ser/IFN-gamma and either IFN-beta ser or IFN-gamma was noted. Although frequency and servity of side effects of IFN-beta ser, IFN-gamma, or the combination were dose related, induction of induced proteins (with exception of influences on tryptophan catabolism) were not a function of dose administered over the 10-fold range. Continued treatment with the combination intravenously three times a week for 4 wk sustained but did not further potentiate, most of the changes in interferon-induced proteins. Thus, IFN-beta ser and IFN-gamma each resulted in effective and essentially equivalent patterns of induction of induced proteins. When combined, however, these IFNs did not result in potentiation of biological response modification in vivo.
authors.affiliation: Department of Human Oncology, University of Wisconsin Clinical Cancer Center, Madison 53792.
authors.forename: J H
authors.initials: JH
authors.lastname: Schiller
authors.forename: B
authors.initials: B
authors.lastname: Storer
authors.forename: D M
authors.initials: DM
authors.lastname: Paulnock
authors.forename: R R
authors.initials: RR
authors.lastname: Brown
authors.forename: S P
authors.initials: SP
authors.lastname: Datta
authors.forename: P L
authors.initials: PL
authors.lastname: Witt
authors.forename: E C
authors.initials: EC
authors.lastname: Borden
mesh_terms: D015088:2',5'-Oligoadenylate Synthetase / Q000032:analysis; D000328:Adult; D000368:Aged; D000920:Antibody-Dependent Cell Cytotoxicity / Q000187:drug effects; D001708:Biopterins / Q000031:analogs & derivatives / Q000097:blood; D004357:Drug Synergism; D005260:Female; D006683:HLA-DQ Antigens / Q000032:analysis; D006684:HLA-DR Antigens / Q000032:analysis; D006801:Humans; D007370:Interferon Type I / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology*; D000068556:Interferon beta-1a; D000068576:Interferon beta-1b; D016899:Interferon-beta; D007371:Interferon-gamma / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology*; D007694:Killer Cells, Natural / Q000187:drug effects / Q000276:immunology; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000187:drug effects / Q000276:immunology; D019798:Neopterin; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology; D014366:Tryptophan Oxygenase / Q000032:analysis; D001613:beta 2-Microglobulin / Q000032:analysis
chemical_list: D006683:HLA-DQ Antigens; D006684:HLA-DR Antigens; D007370:Interferon Type I; D011994:Recombinant Proteins; D001613:beta 2-Microglobulin; D000068576:Interferon beta-1b; D001708:Biopterins; D019798:Neopterin; D016899:Interferon-beta; D007371:Interferon-gamma; D014366:Tryptophan Oxygenase; D015088:2',5'-Oligoadenylate Synthetase; D000068556:Interferon beta-1a