alpha1-Antitrypsin inhibits the lethal response to TNF in mice

Abstract

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.