EFFECTS OF GRANULOCYTE-COLONY-STIMULATING FACTOR AND INTERLEUKIN-2 ONASCITES FORMATION AND THE SURVIVAL-TIME OF NUDE-MICE BEARING HUMAN OVARIAN-CANCER CELLS

The aim of this study was to elucidate the effect of intraperitoneal ( i.p.) instillations of granulocyte-colony-stimulating factor (G-CSF) a nd/or interleukin-2 (IL-2) on ascites formation and the survival time of nude mice with malignant ascites, produced by i.p. inoculation of h uman ovarian cancer cells. When the nude mice were treated with medium alone, ascites was observed in all mice 28 days after tumor inoculati on. When the mice were treated with cis-diamminedichloroplatinum(II) ( cisplatin) alone, G-CSF alone or IL-2 alone, it took 35 days for the a scites to form in all mice. When cisplatin was combined with G-CSF or IL-2, one of ten mice did not form ascites during the observation peri od. Surprisingly, when G-CSF and IL-2 were simultaneously administered , ascites formation was not observed in any mice. Although i.p. treatm ent with cisplatin alone significantly prolonged the survival time, co mpared to medium alone, the lytic activity of spleen cells against HRA cells was significantly suppressed. When G-CSF or IL-2 was combined w ith cisplatin, the suppression by cisplatin was eliminated and subsequ ently resulted in a prolongation of the survival time. When G-CSF was combined with IL-2, both the peritoneal and splenic macrophages/monocy tes were stimulated and the splenic lytic activity was about double th at following treatment with G-CSF alone on IL-2 alone, suggesting that complete inhibition of ascites formation results not only from a sign ificant increase of the peritoneal macrophages but also from enhanceme nt of the lytic activity. Two mice, died from dissemination of tumor i n the abdominal cavity, but eight mice survived without tumor for more than 90 days. As confirmed by monitoring body weight and hematocrit, G-CSF and IL-2 seemed to have no adverse effect. From these results, w e conclude that a combination therapy with G-CSF and IL-2 might be of clinical use for inhibiting large amounts of ascites, which may inhibi t therapeutic effects for ovarian cancer patients.