Independent expression of p55 and p75 interleukin-2 receptors (IL-2R) during intravenous or subcutaneous administration of recombinant interleukin-2 (rIL-2) by T-lymphocytes and natural killer cells.

Abstract

The effects of immunotherapy with recombinant interleukin-2 (rIL-2) on peripheral blood lymphocytes have been a matter of debate. In this study the authors addressed the issue of the biologic effects of two different schedules of rIL-2 administration (i.e., continuous intravenous infusion versus subcutaneous injection) on the expression of the p55 and p75 chains of interleukin-2 receptor (IL-2R). Sixteen patients were studied: 6 patients with a previous diagnosis of acute leukemia entered the study at least +60 days (+63(-)+144 days) after autologous bone marrow transplantation and were treated with continuous rIL-2 infusion; 10 patients with advanced metastatic renal cancer were treated with subcutaneous rIL-2 therapy. In both groups of patients, therapy consisted of two cycles of 5-day rIL-2, and immunologic evaluation was performed two days after completion of the second cycle. Intravenous treatment was associated with a marked increase in CD56+ natural killer (NK) cells expressing the p75 but lacking the p55 IL-2R; however, the absolute number of CD3+ lymphocytes was unchanged, and they showed a low or absent expression of the p55 and negativity for the p75 IL-2R. After subcutaneous rIL-2 therapy, a slight increase in the percentage of NK cells expressing only the p75 IL-2R was shown. CD3+ lymphocytes still retained the p75 IL-2R negative phenotype, however, with a significant increase (> 15%) in p55 IL-2R expression. The absolute number of CD3+ lymphocytes was also significantly increased. Functional tests on the purified CD3+ population indicate that these cells exhibited low values of cytotoxic and proliferative activities in vitro. The authors' data point out that subcutaneous administration of rIL-2 during a 2-week period is associated with a marked increase in T-cells that bear the low affinity p55 IL-2R. These findings could be relevant considering the independent role of lymphokine modulation mediated by the p55 and p75 IL-2R on T- and NK cells.