Comparison of specific adsorbents for tumor necrosis factor-alpha and therapeutic anti-tumor necrosis factor-alpha antibodies: an in vitro sepsis model.
BACKGROUND
Tumor necrosis factor alpha (TNF-alpha), as a key mediator, represents a major point of attack in sepsis. Since it has been shown that systemic anti-TNF-alpha 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-alpha antibodies were investigated in vitro in order to analyze their ability to prevent TNF-alpha induced adhesion of peripheral blood mononuclear cells (PBMCs) at human umbilical vein endothelial cells (HUVECs). Additionally, therapeutical monoclonal anti-TNF-alpha antibodies were proofed for inhibitory effects of TNF-alpha mediated activation of HUVECs.


RESULTS
We have shown, in vitro, that beads coated with polyclonal or monoclonal anti-TNF-alpha 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-alpha treatment by the simultaneous use of beads coated with polyclonal anti-TNF-alpha antibodies. Beads coated with monoclonal anti-TNF-alpha antibodies could even prevent monocyte adhesion within the first 2 hours, and reduced monocyte adhesion to 2% during 6 hours of incubation with TNF-alpha. On the other hand, application of therapeutic anti-TNF-alpha antibodies showed no significant difference compared to the measured monocyte adhesion values of activated endothelial cells.


CONCLUSIONS
Adsorption techniques using specific adsorbents, possibly used in MDS (Microspheres-Based Detoxification System), are efficient in specific reduction of TNF-alpha and pathophysiological consequences, since monocyte adhesion at activated HUVECs was shown to be reduced.
Schwanzer-Pfeiffer
D
D
Christian Doppler Laboratory, Center for Biomedical Technology, Danube University Krems, Krems, Austria. dpfeiffer@donau-uni.ac.at
Mitteregger
R
R
Rossmanith
E
E
Falkenhagen
D
D
D000911:Antibodies, Monoclonal / Q000494:pharmacology*; D002448:Cell Adhesion / Q000187:drug effects; D018929:Cell Culture Techniques; D042783:Endothelial Cells / Q000187:drug effects* / Q000502:physiology; D006801:Humans; D007155:Immunologic Factors / Q000494:pharmacology*; D007963:Leukocytes, Mononuclear / Q000187:drug effects* / Q000502:physiology; D008213:Lymphocyte Activation / Q000187:drug effects / Q000502:physiology; D008863:Microspheres; D018448:Models, Immunological; D018805:Sepsis / Q000276:immunology / Q000628:therapy; D016060:Sorption Detoxification / Q000379:methods*; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology*; D014471:Umbilical Veins / Q000166:cytology
D000911:Antibodies, Monoclonal; D007155:Immunologic Factors; D014409:Tumor Necrosis Factor-alpha