Effect of ranitidine and low-dose interleukin-2 in vitro on NK-cell activity in peripheral blood from patients with liver metastases from colorectal cancer

Abstract

Peripheral venous blood from 12 patients with colorectal cancer and eight healthy volunteers was used to identify the lowest in vitro dose of human, recombinant interleukin-2 (rIL-2) with immunoactivity on NK-cell lysis of K562 tumour cells. Subsequently, this dosage of 200 units/ml rIL-2, which may respond to 10(6) units in vivo, was used alone or in combination with ranitidine (0.02 mg/ml, which may correspond to 100 mg in vivo) to improve in vitro NK-cell activity in peripheral blood from 25 patients with liver metastases from colorectal cancer. A standard 4-hour Cr51-release assay of K562 tumour cells was used for the analyses. Spontaneous NK-cell activity was 19.0% (6.5-33.2), while ranitidine-induced NK-cell activity was 23.6% (7.8-46.2), and without statistical difference from spontaneous activity. Recombinant IL-2-induced NK-cell activity was 37.1% (11.1-71.7) (P < 0.05 compared to spontaneous activity), and rIL-2 plus ranitidine-induced NK-cell activity was 52.7% (18.9-85.6) (P < 0.05 compared to spontaneous and to rIL-2-induced activity, respectively). These results suggest a synergistic increase of low-dose rIL-2-induced NK-cell activity by ranitidine. Therefore, the combination of low-dose rIL-2 and ranitidine may be beneficial to improve post-operative immune competence, and should be considered in future adjuvant treatment regimens of cancer patients.