Blood purification for critical illness: cytokines adsorption therapy.

Blood purification therapies have been clinically applied to treat cytokine-induced pathological effects. The effects of broad-spectrum adsorption using Lixelle (beta2-microglobulin adsorption column; Kaneka Corporation, Osaka, Japan) for the condition of hypercytokinemia in vitro, in an animal model and in humans with sepsis were investigated. We found that Lixelle could selectively adsorb not only beta2-microglobulin but also cytokines composed of glycoproteins in vitro. In addition, Lixelle beads could adsorb not only endotoxin (ET) but also microbial fragments such as peptidoglycan (PG) which is a component of Gram-positive bacteria. Hypercytokinemic rats were connected to a direct hemoperfusion (DHP) system using a mini Lixelle column and time-course changes in plasma levels of inflammatory cytokines were examined. In addition, a Lixelle column was used in direct hemoperfusion in patients with systemic inflammatory response syndrome (SIRS), and the relationship between a decrease in cytokines and clinical course was examined. The increases in plasma levels of IL-6 and tumor necrosis factor-alpha (TNF-alpha) were significantly inhibited in the group treated with the Lixelle column in an animal model. In humans with sepsis, for IL-1beta, IL-1Ra, IL-6, IL-8, and TNF-alpha, the adsorbing rates in vivo before and after the use of the Lixelle column tended to decrease with time. However, the reduction rates at 5 min after the start were 31.4, 39.3, 36.4, 76.2 and 71.6%, respectively, and at 3 h after the start, the rates were 18.0, 17.7, 12.9, 31.8, and 32.9%, respectively. Clinically, their blood pressure increased and they recovered from shock status. These results suggest that SIRS and sepsis with hypercytokinemia can be treated with the DHP using the Lixelle column.