Effect of recombinant human interleukin-2 on the chemotaxis and chemiluminescence of human polymorphonuclear leukocytes

Abstract

Recently, unusual frequency of bacteremia and neutrophil dysfunction during interleukin-2 (IL-2) therapy for advanced cancer has been reported. To determine the cause of this dysfunction, we investigated the effects of recombinant human IL-2 on the chemotaxis and chemiluminescence (CL) response of human polymorphonuclear leukocytes (PMNs) and the effects of tumor necrosis factor-alpha (TNF-alpha), which is elevated after IL-2 administration, on the chemotaxis of human PMNs in vitro. After incubation of various concentrations of IL-2 or TNF-alpha with PMNs obtained from healthy adults, the chemotactic response to stimulation with N-formyl-l-methionyl-l-leucyl-l-phenylalanine was measured by a modified Boyden chamber method. The CL response of PMNs and whole blood was measured by stimulation with non-opsonized zymosan, Staphylococcus aureus or phorbol myristate acetate after 10-minute incubation with IL-2. PMN chemotaxis (IL-2 concentration: 1, 10, 100, 1000 U/ml) and the CL response of PMNs and whole blood (IL-2 concentration: 1, 10, 100 U/ml) were unchanged when compared with the responses of untreated cells. However, PMN chemotaxis was significantly inhibited after incubation with TNF-alpha at concentrations of 1, 10 and 100 U/ml. These results demonstrate that IL-2 has no direct effect on PMN function; however, TNF-alpha which increases in concentration following IL-2 therapy inhibits PMN chemotaxis, indicating that this factor may be a cause of chemotactic defects in PMNs during IL-2 therapy.