Endotoxin Adsorbant Based on Immobilized Human Serum Albumin

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<jats:title>Abstract</jats:title> <jats:p>Extracorporeal apheresis of endotoxins and pro-inflammatory cytokines is still a therapeutic option in the early hyper-inflammatory phase of gram-negative sepsis. There is therefore ongoing interest in adsorber materials suitable for that kind of clinical application. Here we describe lipopolysaccharide (LPS) and cytokine adsorption characteristics of a new adsorbent based on purified human serum albumin (HSA) covalently linked to macroporous polymer beads (iHSA).</jats:p> <jats:p>Multipoint attachment of HSA to acrylic beads via carboxyl groups of the protein resulted in an increased affinity to LPS. In adsorption experiments (adsorbent/plasma ratio 1:3) a 70–80 % reduction of limulus amoebocyte lysate (LAL) activity from 8.59 ± 2.07 EU/ml (mean ± SD) to 1.82 ± 0.77 EU/ml (<jats:italic>S. abortus equi;</jats:italic> n = 40) (p < 0.001) and from 115.13 ± 53.76 EU/ml to 17.70 ± 11.68 EU/ml (<jats:italic>E. coli F583</jats:italic>; n = 6) (p < 0.01) was achieved. iHSA-purified plasma samples showed a decreased capability of inducing cytokine release from peripheral monocytes. Direct haemoperfusion of LPS pre-stimulated whole blood over iHSA resulted in decreased tumour necrosis factor α (TNFα) concentrations (30–40 % reduction) whereas induced levels of interleukin (IL)-β and IL-6 were not affected.</jats:p> <jats:p>Depending on the means of immobilization, iHSA shows higher affinity for LPS than native albumin present in plasma. We demonstrated an efficient removal of LPS from plasma <jats:italic>in vitro</jats:italic>. Adsorption over immobilized HSA appears to be a simple and effective means of removing LPS and perhaps pro-inflammatory cytokines from the circulation.</jats:p>

収録刊行物

  • cclm

    cclm 37 (3), 373-379, 1999-03-01

    Walter de Gruyter GmbH

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