Comparison of Specific Adsorbents for Tumor Necrosis Factor-α and Therapeutic Anti-Tumor Necrosis Factor-α Antibodies: An in Vitro Sepsis Model

Abstract

Background

Tumor necrosis factor alpha (TNF-α), as a key mediator, represents a major point of attack in sepsis. Since it has been shown that systemic anti-TNF-α antibodies do not improve the situation of septic patients, the use of specific adsorption technology in the treatment of sepsis could have beneficial effects.

Methods

Magnetic beads coated with polyclonal or with monoclonal anti-TNF-α antibodies were investigated in vitro in order to analyze their ability to prevent TNF-α induced adhesion of peripheral blood mononuclear cells (PBMCs) at human umbilical vein endothelial cells (HUVECs). Additionally, therapeutical monoclonal anti-TNF-α antibodies were proofed for inhibitory effects of TNF-α mediated activation of HUVECs.

Results

We have shown, in vitro, that beads coated with polyclonal or monoclonal anti-TNF-α antibodies were able to significantly reduce monocyte adhesion. It was possible to decrease monocyte adhesion from nearly 9% to 3% within 2 hours and from 18% to 2% within 6 hours of TNF-α treatment by the simultaneous use of beads coated with polyclonal anti-TNF-α antibodies. Beads coated with monoclonal anti-TNF-α antibodies could even prevent monocyte adhesion within the first 2 hours, and reduced monocyte adhesion to 2% during 6 hours of incubation with TNF-α. On the other hand, application of therapeutic anti-TNF-α antibodies showed no significant difference compared to the measured monocyte adhesion values of activated endothelial cells.

Conclusion

Adsorption techniques using specific adsorbents, possibly used in MDS (Microspheres-Based Detoxification System), are efficient in specific reduction of TNF-α and pathophysiological consequences, since monocyte adhesion at activated HUVECs was shown to be reduced. (Int J Artif Organs 2006; 29: 1140–7)