THE EFFECTS OF INTERLEUKIN-1 THERAPY ON PERIPHERAL-BLOOD GRANULOCYTE FUNCTION IN HUMANS

During a phase I trial of interleukin-1alpha (IL-1alpha) in patients w ith ovarian carcinomas, the effects of this treatment on blood granulo cyte respiratory burst and locomotive responses were examined. Differe nces in baseline granulocyte function in patients as well as dose-rela ted effects of IL-1alpha treatment were observed. Patients enrolled ea rly in the trial (low-dose patients) had significantly lower locomotiv e responses before treatment than their paired controls; these low res ponses normalized after 5 days of continuous-infusion IL-1alpha treatm ent. Patients enrolled later (high-dose patients) had normal locomotiv e responses before treatment and IL-1alpha treatment was associated wi th suppression of responses to selected stimuli at the end of treatmen t. 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 vi tro exposure of either patient or control cells to 150 U/ml IL-1alpha did not alter their locomotive or respiratory burst responses, suggest ing the observed in vivo effects were not mediated directly by IL-1alp ha. Treatment with IL-1alpha is associated with changes in ex vivo gra nulocyte function that are related to the IL-1alpha dose. Treatment wi th low doses of IL-1alpha may provide a means of normalizing abnormal polymorphonuclear leukocyte function in some patients with ovarian mal ignancies.