alpha1-Antitrypsin inhibits the lethal response to TNF in mice.
alpha1-Antitrypsin, an acute-phase reactant in many species, protects significantly against the lethality induced by TNF or endotoxin in mice. The protection is optimal with a single dose of at least 300 microg i.p. or 100 microg i.v. given 2 h before a lethal challenge, either with a low dose of TNF in the presence of galactosamine or a higher dose of murine TNF alone. Under optimal conditions, the drop in body temperature, the release of liver transaminases, and the increase in clotting time are also inhibited. alpha1-Antitrypsin does not protect against a lethal dose of platelet-activating factor. It is suggested that the protection is due to reduced release of platelet-activating factor.
Libert
C
C
Laboratory of Molecular Biology, University of Ghent, Belgium.
Van Molle
W
W
Brouckaert
P
P
Fiers
W
W
D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D001219:Aspartate Aminotransferases / Q000097:blood; D001777:Blood Coagulation / Q000187:drug effects; D001831:Body Temperature / Q000187:drug effects; D004347:Drug Interactions; D005260:Female; D005688:Galactosamine / Q000008:administration & dosage; D008099:Liver / Q000187:drug effects / Q000201:enzymology; D051379:Mice; D008810:Mice, Inbred C57BL; D010972:Platelet Activating Factor / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000008:administration & dosage / Q000037:antagonists & inhibitors* / Q000633:toxicity*; D000515:alpha 1-Antitrypsin / Q000008:administration & dosage / Q000494:pharmacology* / Q000502:physiology
D010972:Platelet Activating Factor; D014409:Tumor Necrosis Factor-alpha; D000515:alpha 1-Antitrypsin; D005688:Galactosamine; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase