Effect of antithrombin III supplementation on inflammatory response in patients with severe sepsis.
Antithrombin III (AT III) is an important inhibitor of thrombin activity, as well as of many other proteases of the coagulation system. AT III administration showed beneficial effects on septic multiple organ dysfunction in clinical and experimental studies. It was the aim of this study to determine whether continuous long-term AT III supplementation alters the systemic inflammatory response in patients with severe sepsis. In a prospective study, 29 surgical patients with severe sepsis were randomly assigned to receive either conventional intensive care treatment (n = 15, control group) or additional AT III supplementation to achieve a plasma AT III activity >120% during a 14 day study period (n = 14, AT III group). Plasma concentrations of interleukin (IL)-6 and IL-8 and of the circulating soluble adhesion molecules sICAM-1 and sE-selectin, as well as of PMN elastase, were determined daily. Additionally, total leukocyte count and C-reactive protein (CRP) were measured daily, and body temperature was registered. Compared to control patients, a down-regulation of plasma IL-6 was observed in the AT III group (p < or = .01). AT III supplementation prevented the continuous increase in sICAM-1 plasma concentration observed in control patients and led to a significant fall in soluble sE-selectin and CRP concentration (p < or = .01). This fall corresponded to a down-regulation of body temperature over time (p < or = .01). There was no AT III effect on IL-8, PMN-elastase concentration, or total leukocyte count. Our results show that long-term AT III supplementation attenuates the systemic inflammatory response in patients with severe sepsis. The down-regulation of IL-6 may also explain the fall in endothelium-derived adhesion molecules and may represent the molecular basis by which AT III exerts its beneficial effects on organ function.
Department of Surgery, Klinikum Grosshadern, Munich, Germany.
D
D
Inthorn
J N
JN
Hoffmann
W H
WH
Hartl
D
D
Mühlbayer
M
M
Jochum
D000328:Adult; D000368:Aged; D000925:Anticoagulants / Q000627:therapeutic use*; D000990:Antithrombin III / Q000627:therapeutic use*; D002097:C-Reactive Protein / Q000032:analysis; D003422:Critical Care; D019040:E-Selectin / Q000097:blood; D005260:Female; D006801:Humans; D007249:Inflammation; D018799:Intercellular Adhesion Molecule-1 / Q000097:blood; D015850:Interleukin-6 / Q000097:blood; D016209:Interleukin-8 / Q000097:blood; D007958:Leukocyte Count; D008297:Male; D008875:Middle Aged; D009102:Multiple Organ Failure / Q000097:blood / Q000276:immunology / Q000628:therapy*; D011446:Prospective Studies; D018805:Sepsis / Q000097:blood / Q000276:immunology / Q000628:therapy*
D000925:Anticoagulants; D019040:E-Selectin; D015850:Interleukin-6; D016209:Interleukin-8; D018799:Intercellular Adhesion Molecule-1; D000990:Antithrombin III; D002097:C-Reactive Protein