The anti-inflammatory properties of antithrombin III: New therapeutic implications

Antithrombin III (AT III) supplementation has proven to be effective in the treatment of disseminated intravascular coagulation. Administration of AT III is also useful for prevention of organ failure in animals challenged wi th endotoxin or bacteria and it increases the survival rate of such animals . Since inhibition of coagulation abnormalities failed to prevent organ fai lure in animals given bacteria, AT III may exert a therapeutic effect indep endent of its anticoagulant effect. This therapeutic mechanism of AT III ha s been explored using an animal model of septicemia. AT III prevented pulmo nary vascular injury by inhibiting leukocyte activation in rats given endot oxin, This effect is mediated by the promotion of endothelial release of pr ostacyclin which inhibits leukocyte activation. Interaction of AT III with heparin-like glycosaminoglycans (GAGs) on the endothelial cell surface appe ars to be important for this effect. Heparin inhibits these therapeutic eff ects of AT III by preventing AT III from interacting with the cell surface heparin-like GAGs, This activity of AT III may explain why AT III prevents organ failure as well as coagulation abnormalities in patients with sepsis, This antiinflammatory activity of AT III may be useful for the treatment o f organ failure such as in ischemia/reperfusion-induced organ dysfunction, in which activated leukocytes play a critical role.