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 with endotoxin or bacteria and it increases the survival rate of such animals. Since inhibition of coagulation abnormalities failed to prevent organ failure in animals given bacteria, AT III may exert a therapeutic effect independent of its anticoagulant effect. This therapeutic mechanism of AT III has been explored using an animal model of septicemia. AT III prevented pulmonary vascular injury by inhibiting leukocyte activation in rats given endotoxin. This effect is mediated by the promotion of endothelial release of prostacyclin which inhibits leukocyte activation. Interaction of AT III with heparin-like glycosaminoglycans (GAGs) on the endothelial cell surface appears to be important for this effect. Heparin inhibits these therapeutic effects 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 of organ failure such as in ischemia/reperfusion-induced organ dysfunction, in which activated leukocytes play a critical role.
Okajima
K
K
Department of Laboratory Medicine, Kumamoto University School of Medicine, Honjo, Japan.
Uchiba
M
M
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use*; D000990:Antithrombin III / Q000627:therapeutic use*; D001778:Blood Coagulation Disorders / Q000517:prevention & control; D004195:Disease Models, Animal; D004211:Disseminated Intravascular Coagulation / Q000188:drug therapy; D006801:Humans; D008213:Lymphocyte Activation; D009102:Multiple Organ Failure / Q000517:prevention & control; D018805:Sepsis / Q000150:complications / Q000188:drug therapy; D015842:Serine Proteinase Inhibitors / Q000627:therapeutic use*
D000893:Anti-Inflammatory Agents; D015842:Serine Proteinase Inhibitors; D000990:Antithrombin III