INTERFERON-GAMMA PROTECTS AGAINST HEPATIC TUMOR-GROWTH IN RATS BY INCREASING KUPFFER CELL TUMORICIDAL ACTIVITY

An increasing number of hepatic resections are being performed as pote ntially curative surgery for malignant liver neoplasms. Hepatectomy an d subsequent liver regeneration produce a local environment that enhan ces growth of microscopic residual tumor. To determine if pretreatment with murine interferon gamma (IFN-gamma) can protect against such enh anced tumor growth, Bufalo rats were randomized to receive a 3-day tre atment of IFN-gamma (50,000 U/qD intraperitoneally) or saline. Groups then underwent intrasplenic injection of 10(6) Morris hepatoma cells, followed 1 hour later by sham (control) or partial hepatectomy (PH) of 70%. PH significantly enhanced tumor growth within the liver (control , 8+/-3 nodules per liver; PH 73+/-12 nodules per liver; P <0.001). Th is enhancement was attenuated by prior administration of IFN-gamma IFN -gamma/PH, 16+/-3; P <.001 vs. PH). Growth factor release and liver re generation were not affected significantly by pretreatment with IFN-ga mma. The effect of IFN-gamma on tumor growth is associated with a sign ificant enhancement of Kupffer cell (KC)-mediated tumoricidal activity (percentage of specific lysis, 55+/-10% control, 78+/-11% IFN-gamma; P <.01) but not lymphocyte-mediated tumoricidal activity. Because micr oscopic residual disease may be present after hepatectomies for cancer , IFN-gamma may be a useful agent in retarding growth of residual tumo rs.