Suppression of natural killer cell cytotoxicity in the peripheral blood of patients receiving interferon therapy.

Lymphoblast interferon (IFN-alpha) was administered to patients with advanced stages of cancer in a phase I drug toxicity trial. IFN-alpha was given i.m. twice daily at 12-h intervals over a 7-day course of therapy in dosages ranging from 1.5 to 100 X 10(6) U/day. A total of 28 patients was studied, including 9 with breast carcinoma, 11 with other solid tumors, and 8 with lymphoid malignancies. Immune cell parameters were determined for each patient before, during, and up to 20 days after therapy. Leukopenia was evident after 1-2 days of IFN-alpha administration, became maximal after 6-7 days of therapy, and then returned to baseline values by day 13 post-therapy. Circulating natural killer (NK) cell activity was found to increase significantly by 2 h after the initial IFN injection, especially in patients receiving the higher dosages. However, most subjects demonstrated a return to baseline NK levels at 24 h despite the continued presence of elevated serum concentrations of IFN. By day 7 of therapy, NK-cell function was markedly depressed. Following cessation of IFN, NK levels rapidly returned to pretherapy baseline values. Changes in K-cell cytotoxic function (ADCC) tended to parallel those of NK-cell function. Although NK/K-cell function was affected by IFN therapy, no change in the percentage of circulating Fc receptor-bearing cells was found. This indicates that the cytotoxic cells were probably present in the circulation, but were not able to express their lytic function.