Induction of natural killer suppressive factor in murine peritoneal cavity by intraperitoneal bolus administration of high-dose cisplatin

Abstract

Background. Intraperitoneal (i.p.) chemotherapy is frequently utilized in patients with advanced gastric cancer or peritoneal dissemination. We investigated whether i.p. administration of cisplatin at high or low doses would impair host local immunity with respect to the induction of natural killer (NK) cell suppressive factor in the murine peritoneal cavity. Methods. Cisplatin was administered at a total dose of 10 mg/kg according to two schedules: high-dose bolus injection (HB; 10 mg/kg) and low-dose consecutive injections (LC; 2 mg/kg daily for 5 days). The supernatant obtained from the peritoneal lavage fluid was added during normal splenocyte-mediated NK cytotoxicity assay. The phenotypes of peritoneal exudate cells were analyzed using anti-F4/80 monoclonal antibody (MAb) and anti-I-A MAb. Results. NK cell activity was significantly inhibited by the supernatant obtained from the HB group 7 days after the administration of cisplatin (40.6% of NK cell activity in controls; P < 0.05). This inhibition was partly restored by prostaglandin E(2) (PGE(2)) antiserum (69.5% of NK cell activity in controls). NK cell activity was not inhibited at any point by exposure to the supernatant of the LC group. I-A(-) peritoneal macrophages were more abundant in the HB group than in the LC group (2.9 x 10(6) vs 4.6 x 10(5) on day 3; P < 0.05). Conclusion. These results suggest that intraperitoneal bolus administration of high-dose cisplatin induces NK suppressive factors, including PGE(2), in the peritoneal cavity, whereas low-dose consecutive administration does not.