title: 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.
authors.affiliation: Surgical Immunology Laboratory, Hvidovre University Hospital, Copenhagen, Denmark.
authors.forename: H J
authors.initials: HJ
authors.lastname: Nielsen
authors.forename: F
authors.initials: F
authors.lastname: Moesgaard
authors.forename: J H
authors.initials: JH
authors.lastname: Hammer
mesh_terms: D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D015179:Colorectal Neoplasms / Q000473:pathology*; D004357:Drug Synergism; D006635:Histamine H2 Antagonists / Q000008:administration & dosage; D006801:Humans; D066298:In Vitro Techniques; D007376:Interleukin-2 / Q000008:administration & dosage; D007694:Killer Cells, Natural / Q000187:drug effects*; D008113:Liver Neoplasms / Q000188:drug therapy* / Q000276:immunology* / Q000556:secondary; D011899:Ranitidine / Q000008:administration & dosage; D011994:Recombinant Proteins / Q000008:administration & dosage
chemical_list: D006635:Histamine H2 Antagonists; D007376:Interleukin-2; D011994:Recombinant Proteins; D011899:Ranitidine