Parameters of interferon action: II. Immunological effects of recombinant leukocyte interferon (IFN-alpha 2) in phase I-II trials.
Twenty-nine patients receiving recombinant interferon (IFN-alpha 2; Schering Plough Corp., Bloomfield, NJ) were studied for changes in natural killer (NK) activity measured by a 4-h 51Cr release assay against K562 cells, and T-cell subsets were determined by indirect immunofluorescence of Leu series monoclonal antibodies (Becton-Dickinson, Mountain View, CA). Seventeen cancer patients received daily i.m. injections of IFN-alpha 2 from 3 to 100 x 10(6) U/day for 28 consecutive days or to tolerance. Twelve of an anticipated 16 melanoma patients have been studied during a phase I trial using the i.v. route with the same recombinant IFN-alpha 2. NK activity rose during the first week of i.m. therapy from 49 +/- 6.5 to 67 +/- 6.2 (mean +/- SE, day 8) at both high (greater than or equal to 30 x 10(6) U/day) and low (less than or equal to 10 x 10(6) U/day) doses. This trend was not observed during therapy by the i.v. route at similar doses, in which NK activity tended to decrease in patients receiving 30 x 10(6) U/day or more. Changes in T-cell subsets were observed in both trials; Leu 3a/2a (helper phenotype/suppressor phenotype) ratio rose twofold in patients receiving i.m. IFN-alpha 2 at higher doses. A rise in Leu-3a+ and a fall in Leu 2a+ T cells account for the change. No change in T-cell subsets was seen in patients treated at low doses (less than or equal to 10(7) U/day) by the i.m. route. By contrast, the Leu 3a/2a ratio fell by 50% in patients who received 30 x 10(6) U/day or more of IFN-alpha 2 by the i.v. route, reflecting a fall in Leu 3a+ cells and a rise in Leu 2a+ cells. Thus, opposite changes in several parameters of immune competence occurred during treatment of patients with melanoma and other cancers, with a single recombinant IFN subspecies given by two different routes.(ABSTRACT TRUNCATED AT 250 WORDS)
D004341:Drug Evaluation; D006801:Humans; D007109:Immunity / Q000187:drug effects; D007273:Injections, Intramuscular; D007275:Injections, Intravenous; D007370:Interferon Type I / Q000627:therapeutic use*; D007694:Killer Cells, Natural / Q000187:drug effects; D008545:Melanoma / Q000276:immunology / Q000628:therapy; D009369:Neoplasms / Q000276:immunology / Q000628:therapy*; D013601:T-Lymphocytes / Q000187:drug effects
D007370:Interferon Type I