title: Endotoxin adsorbent based on immobilized human serum albumin.
abstract: 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). 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 (S. abortus equi; n=40) (p < 0.001) and from 115.13+/-53.76 EU/ml to 17.70+/-11.68 EU/ml (E. coli F583; 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 alpha (TNFalpha) concentrations (30-40% reduction) whereas induced levels of interleukin (IL)-1beta and IL-6 were not affected. 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 in vitro. Adsorption over immobilized HSA appears to be a simple and effective means of removing LPS and perhaps pro-inflammatory cytokines from the circulation.
authors.affiliation: Adsorber Technology Division, Fresenius AG, St. Wendel, Germany. ads@fresenius.de
authors.forename: M
authors.initials: M
authors.lastname: Zimmermann
authors.forename: K
authors.initials: K
authors.lastname: Busch
authors.forename: S
authors.initials: S
authors.lastname: Kuhn
authors.forename: M
authors.initials: M
authors.lastname: Zeppezauer
mesh_terms: D000327:Adsorption; D006801:Humans; D018836:Inflammation Mediators / Q000097:blood; D007375:Interleukin-1 / Q000097:blood; D015850:Interleukin-6 / Q000097:blood; D008070:Lipopolysaccharides / Q000097:blood*; D010956:Plasmapheresis / Q000295:instrumentation*; D012709:Serum Albumin; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D018836:Inflammation Mediators; D007375:Interleukin-1; D015850:Interleukin-6; D008070:Lipopolysaccharides; D012709:Serum Albumin; D014409:Tumor Necrosis Factor-alpha