Immunomodulation with interleukin-2 impruves antitumor effect of chemotherapy and thermotherapy

Peritoneal carcinomatosis is prognostically a very bad sign and common cause of death in patients with gastrointestinal and gynecologic tumors. The aim of this study was to explore and compare different models of locoregional immunochemotherapy, hyperthermial intraperitonal chemotherapy (HIPEC) in animal model of induced peritoneal carcinomatosis in mice. Material and methods: CBA mice were injected with mammary carcinoma (MCa) cells intraperitoneally (ip) inducting peritoneal carcinomatosis. In preventional model biological response modifiers (BRM), interleukin-2 (IL-2) at dose of 4.1 x 104 IU/mouse was injected into abdominal cavity seven and three days before injection of tumor cells, respectively. Immediately after the injection of tumor cells, heated saline at 37°C or at 43°C was injected ip (hyperthermia treatment). Following this mice were ip treated with doxorubicin (DOX) 20 mg kg-1, cisplatin (CIS) 10 mg kg-1, mitomicyn (MIT) 5 mg kg-1, 5- fluorouracil (5-FU) 150 mg kg-1 either separately or in combination of them. In therapeutic model cytostatics were injected on day 5 after injection of tumor cells. Hyperthermia treatment was performed immediately before injection of cytostatic drugs. Results: Results showed significant difference in surviving time (engl. increased life span ; ILS%) of mice pretreated with IL-2 and treated with hyperthermic chemotherapy compared with control: IL-2+ CIS (ILS%=260, 50) ; IL-2+ DOX + CIS (ILS%=200) ; IL-2 + MIT (ILS%=178, 05) ; IL-2 + CDL (ILS%=70, 20) ; IL-2+ DOX (ILS%=67, 92) ; IL-2 + 5-FU (ILS%=62, 69) ; IL-2+ 5-FU+ DOX (ILS%=55, 22). Treatment with IL-2+ 5-FU+ CIS was shown to be toxic to mice since all mice died before control group. Conclusion: The results suggest the synergistic effect of hyperthermia, chemotherapy and immunotherapy ; IL-2 significantly increases antitumor activity of hyperthermic chemotherapy and survival rate of mice with peritoneal carcinomatosis. It is likely that stimulative effect of IL