Endotoxin adsorbent based on immobilized human serum albumin

Area of Science:

• Biomaterials Science
• Immunology
• Sepsis Pathophysiology

Background:

• Extracorporeal apheresis is a therapeutic option for early hyper-inflammatory phase of gram-negative sepsis.
• Ongoing interest exists in developing effective adsorbent materials for clinical applications.

Purpose of the Study:

• To characterize the lipopolysaccharide (LPS) and cytokine adsorption properties of a new adsorbent material: immobilized human serum albumin (iHSA).
• To evaluate the efficacy of iHSA in removing endotoxins and reducing pro-inflammatory mediators in vitro and in whole blood models.

Main Methods:

• Human serum albumin (HSA) was covalently linked to macroporous polymer beads to create iHSA.
• Adsorption experiments were conducted using plasma and whole blood with varying ratios of iHSA.
• Limulus amoebocyte lysate (LAL) activity was measured to quantify endotoxin reduction.
• Cytokine levels (TNF-alpha, IL-1beta, IL-6) were measured after hemoperfusion over iHSA.

Main Results:

• iHSA demonstrated a significant reduction (70-80%) in Limulus amoebocyte lysate (LAL) activity, indicating efficient LPS removal.
• Plasma purified with iHSA showed reduced capacity to induce cytokine release from monocytes.
• Direct hemoperfusion over iHSA resulted in a 30-40% reduction in tumor necrosis factor alpha (TNF-alpha) concentrations.

Conclusions:

• Immobilized human serum albumin (iHSA) exhibits enhanced affinity for LPS compared to native albumin.
• iHSA is an effective and simple means for removing LPS and potentially pro-inflammatory cytokines from circulation.
• This adsorbent shows promise as a therapeutic tool in managing sepsis-induced inflammation.