Interferon gamma protects against hepatic tumor growth in rats by increasing Kupffer cell tumoricidal activity

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Abstract

An increasing number of hepatic resections are being performed as potentially curative surgery for malignant liver neoplasms. Hepatectomy and subsequent liver regeneration produce a local environment that enhances growth of microscopic residual tumor. To determine if pretreatment with murine interferon γ (IFN-γ) can protect against such enhanced tumor growth, Buffalo rats were randomized to receive a 3-day treatment of IFN-γ (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 < .001). This enhancement was attenuated by prior administration of IFN-γ IFN-γ/PH, 16 ± 3; P < .001 vs. PH). Growth factor release and liver regeneration were not affected significantly by pretreatment with IFN-γ. The effect of IFN-γ on tumor growth is associated with a significant enhancement of Kupffer cell (KC)-mediated tumoricidal activity (percentage of specific lysis, 55 ± 10% control, 78 ± 11% IFN-γ, P < .01) but not lymphocyte-mediated tumoricidal activity. Because microscopic residual disease may be present after hepatectomies for cancer, IFN-γ may be useful agent in retarding growth of residual tumors.

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