Effect of antithrombin III on inflammatory immune response in patients with severe sepsis

Full text

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 with a plasma AT III activity >120% during a fourteen day study period (n = 14, AT III group). Plasma Interleukin (IL)-6 and IL-8, and the circulating adhesion molecules ICAM-1 and soluble E-selectin, as well as PMN elastase were determined daily by ELISA. Total leukocyte count and C-reactive protein (CRP) were measured daily and body temperature was registered. Compared to control patients, a downregulation of plasma IL-6, and, to a lesser degree, also of plasma IL-8 was observed in the AT III group (P < 0.05). AT III supplementation prevented the continuous increase in ICAM-1 plasma concentration observed in control patients and lead to a significant fall in serum soluble E-selectin and in CRP concentration (P < 0.05). This fall corresponded to a downregulation of body temperature over time (P < 0.05). There was no AT III effect on PMN elastase concentration or total leukocyte count. Our results show that long-term antithrombin III supplementation attenuates the systemic inflammatory response in patients with severe sepsis.