Endotoxin adsorbent based on immobilized human serum albumin

Extracorporeal apheresis of endotoxins and pro-inflammatory cytokines is st ill a therapeutic option in the early hyper-inflammatory phase of gram-nega tive sepsis. There is therefore ongoing interest in adsorber materials suit able for that kind of clinical application. Here we describe lipopolysaccha ride (LPS) and cytokine adsorption characteristics of a new adsorbent based on purified human serum albumin (HSA) covalently linked to macroporous pol ymer beads (iHSA). Multipoint attachment of HSA to acrylic: beads vie carboxyl groups of the p rotein resulted in an increased affinity to LPS. In adsorption experiments (adsorbent/plasma ratio 1:3) a 70-80 % reduction of limulus amoebocyte lysa te (LAL) activity from 8.59 +/- 2.07 EU/ml (mean +/- SD) to 1.82 +/- 0.77 E U/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-stimul ated whole blood over iHSA resulted in decreased tumour necrosis factor or (TNF alpha) concentrations (30-40 % reduction) whereas induced levels of in terleukin (IL)-1 beta and IL-6 were not affected. Depending on the means of immobilization, iHSA shows higher affinity for LP S than native albumin present in plasma. We demonstrated an efficient remov al of LPS from plasma in vitro. Adsorption over immobilized HSA appears to be a simple and effective means of removing LPS and perhaps pro-inflammator y cytokines from the circulation.