Comparison of a cytokine adsorbing column and an endotoxin absorbing column for the treatment of experimental endotoxemia

doi:10.1016/j.transci.2008.11.002

Transfusion and Apheresis Science

Volume 40, Issue 1, February 2009, Pages 55-59

https://doi.org/10.1016/j.transci.2008.11.002 Get rights and content

Abstract

The present study compared the effects of direct hemoperfusion (DHP) using a cytokine absorbing (CTR) column with those using an endotoxin absorbing (PMX) column with endotoxin-induced shock in rats. Thirty-six rats were injected intravenously with endotoxin (15 mg/kg), and then allocated into one of the following three groups: control group, treated without CTR; PMX group, treated with a PMX column for 120 min; CTR group, treated with a CTR column for 120 min. The present study showed that CTR treatment decreased the mortality rate 8 h after endotoxin injection and inhibited inflammatory responses (cytokine, hemodynamics and acidosis) similar to PMX treatment.

Introduction

Endotoxemia is a major cause of sepsis. Circulating endotoxins induce the activation of complement and the release of proinflammatory cytokines, such as tumor necrosis factor (TNF)-alpha and interleukin (IL)-1beta [1]. The proinflammatory cytokines, particularly TNF-alpha, IL-1beta and IL-6, and nitric oxide induced by endotoxin can decrease systemic vascular resistance, resulting in marked hypotension [2], [3]. The combination of hypotension and microvascular occlusion results in tissue ischemia and ultimately leads to multiple organ failure [4]. Several recent reports showed that direct hemoperfusion (DHP) using the endotoxin absorbing column improved hemodynamics and cardiac function to endotoxemia and endotoxic shock in patients [5], [6], [7].

Our previous studies demonstrated that a new cytokine adsorbing column, CTR, effectively adsorbed small- to medium-sized proteins, such as cytokines, in vitro and that DHP using a CTR column reduced mortality and inhibited inflammatory responses in endotoxemic rats [8], [9]. However, we did not evaluate whether DHP using a CTR column or an endotoxin absorbing column has more beneficial effects after endotoxin injection. The present study was performed to compare the effects of DHP using a CTR column with those using an endotoxin absorbing column on mortality and inflammatory responses in rats with endotoxin-induced shock.

Section snippets

Materials and methods

Thirty-six male Wistar rats, weighing 384 ± 16 g (mean ± SD), were used in this study. The experimental protocol was approved by the Animal Care Committee of our institute, and the care and handling of the animals were in accordance with the guidelines of the National Institute of Health.

The cytokine adsorbing column, CTR developed by KANEKA Corporation (Osaka, Japan) is composed of porous cellulose beads to which a hydrophobic organic compound with a hexadecyl alkyl chain has been covalently

Hemodynamics and mortality rate

There were no significant differences in baseline HR or SAP among the groups (Fig. 1). Four hours after endotoxin injection, the SAPs was reduced in group C, but not in group PMX or CTR. The SAP in group CTR was not significantly different from that in group PMX. The mortality rates at 8 h after the endotoxin injection were 92%, 33% and 17% in groups C, PMX and CTR, respectively (Fig. 2). The mortality rates of group PMX and CTR were significantly lower than that of group C. The mortality rate

Discussion

Control column treatment in our experiments produced a high mortality rate and a large increase in plasma cytokine concentration after the endotoxin injection. PMX and CTR treatments carried out for 120 min after the endotoxin injection, markedly reduced the high mortality rate and inhibited proinflammatory cytokine responses in endotoxin-exposed rats. These effects after the endotoxin injection were not significantly different between PMX and CTR treatment groups.

Our previous studies

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Comparison of a cytokine adsorbing column and an endotoxin absorbing column for the treatment of experimental endotoxemia

Abstract

Introduction

Section snippets

Materials and methods

Hemodynamics and mortality rate

Discussion

J Am Coll Cardiol

Am J Surg

The immunopathogenesis of sepsis

Nature

Tumor necrosis factor-alpha-induced caspase activation mediates endotoxin-related cardiac dysfunction

Crit Care Med

Endotoxin and tumor necrosis factor challenges in dogs simulate the cardiovascular profile of human septic shock

J Exp Med

Effect of an endotoxin-removing column containing immobilized polymyxin B fiber in a patient with septic shock from gram-positive infection

Acta Anaesthesiol Scand