AN ACQUIRED CHEMOTACTIC DEFECT IN NEUTROPHILS FROM PATIENTS RECEIVING INTERLEUKIN-2 IMMUNOTHERAPY

Bacterial sepsis is a frequent complication in patients with cancer who are receiving high doses of interleukin-2. We evaluated the function of neutrophils from such patients to determine whether there was any abnormality in this form of host defense. Before interleukin-2 therapy, neutrophils from 31 patients with metastatic cancer were normal in assays of random migration and chemotaxis. Superoxide production, phagocytosis, secretion of granule proteins, and bactericidal activity were also normal. Neutrophils from the patients near the end of the first course of interleukin-2 had severely impaired chemotaxis in response to a formylated peptide stimulus (mean [±SEM], 49.6±7.4 percent of base line; P<0.001). The defect in chemotaxis improved 5 to 10 days after patients completed the first course of interleukin-2 therapy but recurred toward the end of the second course of such therapy (35.3±6.9 percent of base line; P<0.001). The chemotactic response to a second stimulus (zymosan-activated serum) was also abnormal, but random migration, superoxide production, bactericidal activity, and the secretion of neutrophil granule constituents remained normal or increased throughout treatment with interleukin-2. We conclude that patients who receive interleukin-2 immunotherapy acquire an acute, profound, and reversible defect in neutrophil chemotaxis that may contribute to the high morbidity resulting from bacterial infections in these patients. INTERLEUKIN-2 is a 15,000-dalton protein that is produced and secreted by activated T lymphocytes and has profound effects on the immune response.1,2 One of these effects is the induction of lymphokine-activated killer cells that are able to lyse a broad spectrum of malignant cells in vitro.3 Because extensive studies in tumor-bearing animals and initial trials of high doses of interleukin-2 and lymphokine-activated killer cells in humans with metastatic cancer demonstrated marked tumor regression,4 5 6 7 a large-scale multi-institutional trial of such therapy was undertaken. These studies largely confirmed the observations that immunotherapy with interleukin-2 and lymphokine-activated killer cells can lead to tumor… © 1990, Massachusetts Medical Society. All rights reserved.