The effects of interleukin-1 therapy on peripheral blood granulocyte function in humans
During a phase I trial of interleukin-1α (IL-1α) in patients with ovarian carcinomas, the effects of this treatment on blood granulocyte respiratory burst and locomotive responses were examined. Differences in baseline granulocyte function in patients as well as dose-related effects of IL-1α treatment were observed. Patients enrolled early in the trial (low-dose patients) had significantly lower locomotive responses before treatment than their paired controls; these low responses normalized after 5 days of continuous-infusion IL-1α treatment. Patients enrolled later (high-dose patients) had normal locomotive responses before treatment and IL-1α treatment was associated with suppression of responses to selected stimuli at the end of treatment. Pretreatment respiratory burst responses in both low-and high-dose patient groups were essentially normal, but the rates of granulocyte H2O2 production following phorbol myristate acetate stimulation became significantly less than control values at the end of treatment. In vitro exposure of either patient or control cells to 150 U/ml IL-1α did not alter their locomotive or respiratory burst responses, suggesting the observed in vivo effects were not mediated directly by IL-1α. Treatment with IL-1α is associated with changes in ex vivo granulocyte function that are related to the IL-1α dose. Treatment with low doses of IL-1α may provide a means of normalizing abnormal polymorphonuclear leukocyte function in some patients with ovarian malignancies.