Effects of Extracorporeal Treatment With Lixelle on the Mortality and Inflammatory Responses to Endotoxin‐Induced Shock in Rats

Abstract

Endotoxemia and endotoxic shock are common problems in intensive care units and are associated with a very high mortality. Several previous studies have shown that Lixelle, which absorbs beta2-microglobulin for the treatment of dialysis-related amyloidosis, is also useful for the adsorption of inflammatory cytokines and endotoxins. The current study examined the use of Lixelle and its effects on the mortality and inflammatory responses to endotoxin-induced shock in rats. Male Sprague-Dawley rats were anesthetized and assigned to one of four groups (N = 13 per group): Escherichia coli endotoxin (15 mg/kg, i.v.) alone (endotoxemic); direct hemoperfusion apheresis without Lixelle for 120 min (direct hemoperfusion (DHP) alone); Lixelle treatment with Lixelle for 120 min immediately after endotoxin injection (Lixelle treatment); or Lixelle treatment with Lixelle for 120 min 2 h after endotoxin injection (Lixelle post-treatment). Hemodynamics and plasma lactate and cytokine concentrations were measured during observation. Mortality was assessed up to 8 h after the endotoxin injection. The mortality rates at 8 h after endotoxin injection were 92%, 85%, 23% and 46% for the endotoxemic, DHP-alone, Lixelle treatment, and Lixelle post-treatment groups, respectively. Elevated plasma cytokine concentrations were less conspicuous in the Lixelle treatment group than in the other three groups. Thus, Lixelle treatment drastically reduced the high mortality and the inflammatory responses in endotoxin-exposed rats. Moreover, Lixelle post-treatment also suppressed hypotension and a high mortality, although the inflammatory responses were the same as for endotoxin alone. These findings indicate that Lixelle treatment might be an effective therapy for endotoxemia and endotoxic shock.