The effects of interleukin-1 therapy on peripheral blood granulocyte function in humans

Abstract

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.