Modulation of natural killing activity by lymphoblastoid interferon in cancer patients.
The in vivo and in vitro effects of partially purified human lymphoblastoid alpha-interferon (alpha-IFN) on natural killing (NK) and antibody-dependent cellular cytotoxicity (ADCC) of peripheral blood were tested in 17 cancer patients. The study tested single doses of alpha-IFN (part A), and repeated, incremental doses (15 over 5 weeks; part B). The initial response to alpha-IFN was a decline of NK and ADCC activity, reaching a nadir at 12 h. The decline was found to be partly related to nonadherent suppressor cells. The NK activity generally returned to or exceeded baseline within 24-48 h and stayed elevated for a week or more after a single injection. Interestingly, the decline in NK activity was not unique to the first injection, but was found even in chronic treatment 12 h after alpha-IFN injection. Dose-response studies showed that maximum stimulation was achieved by the end of the first week, when it was greater for patients receiving higher doses of alpha-IFN. However, patients who received repeated injections at lower doses were able to sustain this stimulation, whereas those who received higher doses were not. Very low doses (0.5 mU/m2) appeared to be maximally efficient. IFN administration to the same group of cancer patients seemed to have similar effects on ADCC against tumor cells. Furthermore, our study has shown that cells responsive in vitro to alpha-IFN (drawn prior to treatment) showed an increase in NK activity similar to that after in vivo administration of alpha-IFN, indicating a simple predictor of patients' responsiveness to IFN treatment. Taken together, these findings indicate that in vivo administration of alpha-IFN results in a dose-dependent augmentation of NK and ADCC activity in cancer patients.
D000328:Adult; D000920:Antibody-Dependent Cell Cytotoxicity / Q000187:drug effects; D002460:Cell Line; D002860:Chromium Radioisotopes; D005260:Female; D006801:Humans; D007370:Interferon Type I / Q000494:pharmacology*; D007694:Killer Cells, Natural / Q000187:drug effects*; D007958:Leukocyte Count; D008214:Lymphocytes / Q000187:drug effects; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000276:immunology*; D013997:Time Factors
D002860:Chromium Radioisotopes; D007370:Interferon Type I