Comparative study on the effects of recombinant alpha-2 interferon on immune function in patients with disseminated...

Fifteen patients with disseminated melanoma were treated by intravenous administration of recombinant alpha-2 interferon (rIFN-alpha 2) on 5 consecutive days every 2 weeks. Immunological studies on approximately 50% of the patients revealed no significant changes in lymphocyte numbers or T-cell subsets. Natural killer (NK) activity against the K562 target cell and a melanoma cell was increased in the first treatment cycle, but in subsequent treatment cycles it tended to decrease against the melanoma cell and to show either no change or moderate increases against the K562 target cell. Interleukin-2 (IL-2) production from mitogen-stimulated lymphocytes was decreased in most patients in each treatment cycle. This also applied to immunoglobulin production in vitro from pokeweed mitogen (PWM)-stimulated B and T cells. The latter was not due to the induction of radiation-sensitive suppressor T cells and may reflect effects on B cells or helper T cells. The repeated inhibition of IL-2 production with each cycle of treatment and the decrease in NK activity against the melanoma target cells after the first treatment cycle contrasted with the return to at or above pretreatment values of these tests when rIFN-alpha A was given intramuscularly on an alternate-day basis. It is suggested that these effects may be due to the relatively greater increase in endogenous cortisol production at the beginning of each treatment cycle in patients given rIFN-alpha 2 intravenously compared to that observed in patients treated with rIFN-alpha A on alternate days intramuscularly. Immunosuppression resulting from the increase in cortisol production may be one of the factors accounting for the low tumor response rate of patients in this study and may emphasize the possible importance of the schedule of rIFN-alpha administration for obtaining optimal antitumor responses.