Increase in soluble interleukin-2 receptor and neopterin serum levels during immunotherapy of cancer with interleukin-2

Abstract

Both immunostimulatory and immunosuppressive events would occur during the immunotherapies of cancer, including interleukin 2 (IL-2) therapy. The marked increase in soluble IL-2 receptor (SIL-2R) levels during IL-2 therapy could represent a potentially negative biological effect, because of the receptor's capacity to bind IL-2 and compete for it with IL-2 cell surface receptor. Since it has been observed that macrophages stimulate in vitro the release of SIL-2R, a study was started to evaluate in vivo the role of macrophages in IL-2-induced SIL-2R rise by measuring neopterin, which is a marker of macrophage activity. The study included 9 advanced renal cancer patients, treated subcutaneously with IL-2 at 1.8 x 10(6) IU/m2 twice daily for 5 days/week for 6 weeks. Both SIL-2R and neopterin serum mean levels significantly increased during IL-2 treatment, and the highest concentrations were reached on the second week of therapy. SIL-2R rise was significantly correlated to that of neopterin. This study, by showing a positive correlation between SIL-2R and neopterin rise, would suggest a macrophage involvement in the stimulation of SIL-2R release during IL-2 immunotherapy of cancer.