Adenoviral infection decreases mortality from lipopolysaccharide-induced liver failure via induction of TNF-alpha tolerance.
Effects of adenoviral infection on in vivo responses to LPS mediated by TNF-alpha were evaluated in a murine model. Adenovirus-infected mice showed decreased mortality from fulminant hepatitis induced by administration of LPS or staphylococcal enterotoxin B in the presence of D-galactosamine. Importantly, TNF-alpha resistance genes within adenoviral E3 region were not required, because E1,E3-deleted vectors showed similar effects. Adenovirus-infected mice exhibited higher TNF-alpha levels after LPS stimulation, no difference in TNFR1 expression, and similar mortality from Fas-induced fulminant hepatitis. Decreased production of IL-6 and KC in response to exogenous TNF-alpha, in addition to protection from TNF-alpha, suggested that adenoviral infection results in TNF-alpha tolerance.
Yarovinsky
Timur O
TO
Department of Internal Medicine, Division of Pulmonary, Critical Care, and Occupational Medicine, University of Iowa, 100 EMRB, Iowa City, IA 52242, USA. timur-yarovinsky@uiowa.edu
Powers
Linda S
LS
Butler
Noah S
NS
Bradford
Mary A
MA
Monick
Martha M
MM
Hunninghake
Gary W
GW
D000258:Adenovirus Infections, Human / Q000276:immunology* / Q000401:mortality; D000260:Adenoviruses, Human / Q000276:immunology; D000818:Animals; D015703:Antigens, CD / Q000096:biosynthesis; D001323:Autoantibodies / Q000633:toxicity; D002460:Cell Line; D004195:Disease Models, Animal; D005260:Female; D005688:Galactosamine / Q000633:toxicity; D006801:Humans; D007108:Immune Tolerance / Q000502:physiology*; D007274:Injections, Intraperitoneal; D007275:Injections, Intravenous; D008070:Lipopolysaccharides / Q000633:toxicity*; D008099:Liver / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D017093:Liver Failure / Q000276:immunology* / Q000401:mortality* / Q000473:pathology / Q000517:prevention & control; D051379:Mice; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D018124:Receptors, Tumor Necrosis Factor / Q000096:biosynthesis; D047888:Receptors, Tumor Necrosis Factor, Type I; D016019:Survival Analysis; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis / Q000502:physiology*; D015854:Up-Regulation / Q000276:immunology; D019014:fas Receptor / Q000276:immunology
D015703:Antigens, CD; D001323:Autoantibodies; D008070:Lipopolysaccharides; D018124:Receptors, Tumor Necrosis Factor; D047888:Receptors, Tumor Necrosis Factor, Type I; D014409:Tumor Necrosis Factor-alpha; D019014:fas Receptor; D005688:Galactosamine