Physiological Response to Superantigen-Adsorbing Hemoperfusion in Toxin-Concentration-Controlled Septic Swine

Abstract

Background/Aims: Superantigens are suspected of being potent initiators of gram-positive sepsis, and new therapies for superantigen elimination are required. The effects of hemoadsorption with a superantigen-adsorbing device (SAAD) were evaluated in septic swine. Methods: Toxic shock syndrome toxin-1 (TSST-1) was infused, and blood concentration was maintained at the clinical level for 6 h. Endotoxin was then infused to induce lethal shock. All animals were hemoperfused with SAAD or a control column for 8 h and changes in pathological parameters and mortality were examined. Results: Animals perfused with SAAD had a highly significant (p < 0.01) survival advantage compared with control groups at 24 h after initiation of the TSST-1 infusion. SAAD also suppressed the increase in the arteriovenous shunt ratio and decrease of partial arterial oxygen pressure at 6 h after TSST-1 infusion initiation. Conclusion: We suggest that there is a potential application of SAAD in treating superantigen-induced respiratory dysfunction and sepsis.

Direct Hemoperfusion with a Cytokine-Adsorbing Device for the Treatment of Persistent or Severe Hypercytokinemia: A Pilot Study

“…Four kinds of cytokine adsorbers have thus far been developed: the CYT-860 [8,9,13,14] , Cytosorb [15,16] , CTR [17,18] , and MPCF-X [19] ; but there are very few clinical reports of these four adsorbers [18] . The CYT-860, which was evaluated in the present study, was originally developed as an exotoxin adsorber and found during the course of development to adsorb cytokines as well.…”

“…They also found that this treatment inhibited increases in the blood bacterial count, plasma exotoxin level, and plasma IL-6 level [13] . Miwa et al [14] performed CYT-860-DHP treatment in a swine sepsis model prepared by the administration of toxic shock syndrome toxin-1 (TSST-1) and endotoxin, and reported significant improvement in the survival rate in the treatment group compared with the control group 24 h after the initiation of treatment (60 vs. 0%, p ! 0.01).…”

Can Modification of Renal Replacement Therapy Improve the Outcome of Patients with Systemic Inflammatory Response Syndrome?

“…The question arises as to whether new sorbents can be developed to target the removal of specifi c pathogenic toxins and other infl ammatory mediators. Recent interest has centred on Gram-positive sepsis and the role of toxic shock syndrome toxin-1 (TSST-1), a superantigenic protein produced by Staphylococcus aureus which has been shown to produce multiple organ dysfunction in animal models similar to the human systemic infl ammatory response syndrome [10] . Preliminary animal experiments have shown improved animal survival, using specially developed haemoperfusion sorbents designed to remove Gram-positive peptidoglycans, TSST-1 and Gram-negative endotoxins in a model of endotoxin/TSST-1-induced multiple organ dysfunction.…”

Specific immuno capturing of the Staphylococcal superantigen toxic‐shock syndrome toxin‐1 in plasma

“…It has been demonstrated that devices capable of capturing toxins from plasma resulted in reduced mortality among septic animals compared to the untreated animals (Fenwick et al, 2003;Miwa et al, 2003Miwa et al, , 2006bTaniguchi et al, 2006). In these experiments a toxin-concentration-controlled animal model was used in which pigs were infused with TSST-1, and monitoring was performed for both the infusion period and a subsequent 1-h post-infusion period.…”

“…Various adsorption devices have been developed that were shown to bind to endotoxins, cytokines and enterotoxins including TSST-1. Treatment of animals, with experimental sepsis and/or endotoxemia, using these devices resulted in reduced mortality compared with the animals which were left untreated (Fenwick et al, 2003;Miwa et al, 2003Miwa et al, , 2006bTaniguchi et al, 2006). A drawback of the adsorption devices used is that they bind a variety of small proteins which are not strictly defined and may also include beneficial molecules.…”