EFFECTS OF INTRAPERITONEAL RECOMBINANT INTERLEUKIN-1-BETA IN INTRAPERITONEAL HUMAN OVARIAN-CANCER XENOGRAFT MODELS - COMPARISON WITH THE EFFECTS OF TUMOR-NECROSIS-FACTOR

The effect of intraperitoneal (i.p.) injection of recombinant human interleukin-1-beta (rhIL-1-beta) was studied in three i.p. nude mouse xenograft models of human ovarian cancer (HU, OS, and LA). Intraperitoneal rhIL-1-beta administration led to a dose dependent replacement of peritoneal ascitic tumour with solid tumours attached to the peritoneum and intraabdominal viscera in two (HU and LA) out of the three xenograft models. In the third xenograft model (OS), low doses of rhIL-1-beta (1O ng day) promoted micrometastatic peritoneal implants of tumour, but higher doses of rhIL-1-beta (1-mu-g day) had a marked antitumour effect This was due to direct cytotoxicity for tumour cells and was not related to peritoneal neutrophil influx induced by rhIL-1-beta. Recombinant human TNF (rhTNF) also promoted tumour implantation in all three xenograft models, but its antitumour effects differed from rhIL-1-beta. TNF increased the survival of HU and LA bearing mice, but had no antitumour effect in the OS xenograft model. Analysis of peritoneal fluid and tumour xenografts showed that TNF induced murine IL-1 in the tumour bearing mice. The magnitude of IL-1 induction indicated that TNF induced IL-1 did not contribute significantly to its effects.