Hyporesponsiveness of SPRET/Ei mice to lethal shock induced by tumor necrosis factor and implications for a TNF-based antitumor therapy.
Tumor necrosis factor (TNF) is a central mediator in lethal shock and an interesting cytokine for anticancer therapy. To inhibit TNF-induced lethal shock, it is important to identify protective genes. Here we demonstrate that the SPRET/Ei mouse strain, derived from Mus spretus, exhibits an extremely dominant resistance to TNF-induced lethal inflammation. An interspecific backcross experiment revealed that the TNF hyporesponse is linked to loci on chromosomes 2, 6, and 11. Treatment of inoculated tumors with TNF and IFN-gamma leads to regression and a highly reduced toxicity in (C57BL/6 x SPRET/Ei)F(1) mice.
Staelens
Jan
J
Department of Molecular Biomedical Research, Flanders Interuniversity Institute for Biotechnology and Ghent University, K. L. Ledeganckstraat 35, B-9000 Ghent, Belgium.
Wielockx
Ben
B
Puimège
Leen
L
Van Roy
Frans
F
Guénet
Jean-Louis
JL
Libert
Claude
C
D000818:Animals; D016923:Cell Death / Q000187:drug effects; D004351:Drug Resistance; D005260:Female; D005347:Fibroblasts / Q000166:cytology / Q000187:drug effects; D008040:Genetic Linkage; D007371:Interferon-gamma / Q000627:therapeutic use; D015850:Interleukin-6 / Q000096:biosynthesis; D017737:Macrophages, Peritoneal / Q000187:drug effects / Q000276:immunology; D008297:Male; D008546:Melanoma, Experimental / Q000188:drug therapy; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D009115:Muridae; D011994:Recombinant Proteins / Q000627:therapeutic use / Q000633:toxicity; D012769:Shock / Q000209:etiology*; D014409:Tumor Necrosis Factor-alpha / Q000627:therapeutic use / Q000633:toxicity*
D015850:Interleukin-6; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma