COMPARATIVE INVIVO AND INVITRO ACTIVATION OF HUMAN NATURAL-KILLER CELLS BY 2 RECOMBINANT ALPHA-INTERFERONS DIFFERING IN ANTIVIRAL ACTIVITY

  • 1 January 1984
    • journal article
    • research article
    • Vol. 44  (7) , 3135-3139
Abstract
Natural kill (NK) cell activation by 2 interferon-.alpha. subtypes, interferon-.alpha.A and interferon-.alpha.D, was examined in vitro and in vivo in 8 cancer patients. When assessed in vitro, NK cells in 6 of 8 patients lysed K562 [human leukemia] cells to a greater extent when incubated with interferon-.alpha.A (1 ng/ml) than with the same concentration of interferon-.alpha.D. When patients were evaluated collectively, no significant difference was detectable in the effectiveness of the 2 subtypes in enhancing NK cell activity. Patients received the same interferons given as 4 injections which were randomized with respect to subtype and were separated by intervals of .gtoreq. 6 days. NK cell activity was consistently elevated in peripheral mononuclear cells sampled 24 h but not 7 days after injection as compared to peripheral mononuclear cells sampled just prior to each injection (P < 0.001 for both subtypes). At a given dose level, both interferon subtypes resulted in comparable NK cell activation. A negative correlation existed between the amount of interferon administered and the magnitude of enhancement (P < 0.05). In 16 separate paired determinations, there were 8 in which NK cell activity was lower after the 2nd injection of an interferon dose than after the 1st injection of the same dose (15 or 45 .mu.g, irrespective of subtype), and 8 in which the alternate pattern occurred. Repeated injection in the same patient of one or the other dose resulted in no consistent changes in the extent of NK cell stimulation. Since the 2 interferons have a 20-fold difference in specific antiviral activity for human amnion cells and up to an 80-fold difference in human fibroblasts, either different mechanisms are involved in antiviral and NK cell-stimulatory activity, or activities of these 2 subtypes for cells of different histogenesis vary. Greater NK cell-stimulatory activity therefore occurred at the lowest tested doses, a dose which was < 10% of previously reported maximally tolerated doses of these interferons.