Protection by alpha 1-acid glycoprotein against tumor necrosis factor-induced lethality.
We here report that alpha 1-acid glycoprotein, a typical acute phase protein, protects mice from lethal shock induced by tumor necrosis factor (TNF) or endotoxin. The protection is observed both in normal and in galactosamine-sensitized mice. Optimal desensitization requires at least 3 mg alpha 1-acid glycoprotein administered 2 h before the lethal challenge. Under these conditions, complete inhibition of all TNF-induced metabolic changes was observed: fall in body temperature, release of liver transaminases, enhanced clotting time, and mortality. The known platelet aggregation-inhibitory activity of alpha 1-acid glycoprotein provides a possible explanation for this protective capacity.
Libert
C
C
Laboratory of Molecular Biology, University of Gent, Belgium.
Brouckaert
P
P
Fiers
W
W
D000818:Animals; D005260:Female; D005688:Galactosamine / Q000633:toxicity; D008070:Lipopolysaccharides / Q000633:toxicity; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D009961:Orosomucoid / Q000494:pharmacology*; D014409:Tumor Necrosis Factor-alpha / Q000633:toxicity*
D008070:Lipopolysaccharides; D009961:Orosomucoid; D014409:Tumor Necrosis Factor-alpha; D005688:Galactosamine