title: Interferon gamma protects against hepatic tumor growth in rats by increasing Kupffer cell tumoricidal activity.
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 gamma (IFN-gamma) can protect against such enhanced tumor growth, Buffalo rats were randomized to receive a 3-day treatment 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 < .001). This enhancement was attenuated by prior administration of IFN-gamma IFN-gamma/PH, 16 +/- 3; P < .001 vs. PH). Growth factor release and liver regeneration were not affected significantly by pretreatment with IFN-gamma. The effect of IFN-gamma 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-gamma, P < .01) but not lymphocyte-mediated tumoricidal activity. Because microscopic residual disease may be present after hepatectomies for cancer, IFN-gamma may be useful agent in retarding growth of residual tumors.
authors.affiliation: Department of Surgery, Memorial Sloan-Kettering Cancer Center, New York, NY, USA.
authors.forename: H M
authors.initials: HM
authors.lastname: Karpoff
authors.forename: C
authors.initials: C
authors.lastname: Tung
authors.forename: B
authors.initials: B
authors.lastname: Ng
authors.forename: Y
authors.initials: Y
authors.lastname: Fong
mesh_terms: D000818:Animals; D003602:Cytotoxicity, Immunologic / Q000187:drug effects*; D006498:Hepatectomy; D007371:Interferon-gamma / Q000494:pharmacology* / Q000627:therapeutic use; D007728:Kupffer Cells / Q000187:drug effects* / Q000276:immunology; D008114:Liver Neoplasms, Experimental / Q000517:prevention & control*; D008115:Liver Regeneration / Q000187:drug effects; D008214:Lymphocytes / Q000187:drug effects / Q000276:immunology; D008297:Male; D051381:Rats; D011915:Rats, Inbred BUF
chemical_list: D007371:Interferon-gamma