ALPHA(1)-ANTITRYPSIN INHIBITS THE LETHAL RESPONSE TO TNF IN MICE

alpha(1)-Antitrypsin, an acute-phase reactant in many species, protect s significantly against the lethality induced by TNF or endotoxin in m ice. The protection is optimal with a single dose of at least 300 mu g i.p. or 100 mu g i.v. given 2 h before a lethal challenge, either wit h 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 temper ature, the release of liver transaminases, and the increase in clottin g time are also inhibited, alpha(1)-Antitrypsin does not protect again st a lethal dose of platelet-activating factor. It is suggested that t he protection is due to reduced release of platelet-activating factor.