In vitro cell culture systems as the basis for an extracorporeal blood purification strategy in multiorgan failure treatment.
Multiorgan failure (MOF) based on septic processes is very common but prognostically an extremely severe disease that has to be treated exclusively under intensive care conditions. Extracorporeal blood purification (ECBP) using specific and efficient systems such as the microspheres based detoxification system (MDS) (Artif Organs 1996;20:420) could improve significantly the situation of MOF in terms of the efficient removal of endotoxins as well as key mediators such as tumor necrosis factor alpha (TNF alpha). The purpose of the study was to test the effectiveness of endotoxin and cytokine removal to blunt cellular response. In terms of the in vitro principle methodology, isolated peripheral blood mononuclear cells (PBMC) were incubated with endotoxins and a selective endotoxin adsorbent, which was added at various times (immediately or 30, 60, 120, 240, or 360 min) after the onset of incubation. TNF alpha release of monocytes was measured following a standard procedure after 20 h. Human TNF alpha was incubated with cultured human endothelial cells with and without a specific TNF alpha adsorbent (polyclonal antibodies coated on polystyrene particles). The results showed that after the initial addition of endotoxins, the activation of monocytes can be stopped within 120 min by addition of endotoxin adsorbents. In addition, specific TNF alpha adsorbents are able to prevent intercellular adhesion molecule 1 (ICAM-1) expression of endothelial cells, therefore avoiding activation of endothelial cells. In conclusion, cell culture models are suitable to simulate cell interaction in MOF. Specific adsorbents are able to reduce or block pathophysiologically relevant cell interactions, and the time frame for effective ECBP seems to be very short, and therefore, efficiency must be high.
Mitteregger
R
R
Centre of Biomedical Technology, Danube-University Krems, Austria. mitteregger@zbmt.donau-uni.ac.at
White
A
A
Weber
C
C
Rossmanith
E
E
Mohr
T
T
Micksche
M
M
Falkenhagen
D
D
D002478:Cells, Cultured; D003636:DEAE-Cellulose; D004730:Endothelium, Vascular / Q000166:cytology; D004731:Endotoxins / Q000097:blood* / Q000302:isolation & purification; D006464:Hemoperfusion / Q000379:methods*; D006801:Humans; D007163:Immunosorbent Techniques; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D007963:Leukocytes, Mononuclear; D008863:Microspheres; D009102:Multiple Organ Failure / Q000382:microbiology / Q000628:therapy*; D014409:Tumor Necrosis Factor-alpha / Q000302:isolation & purification
D004731:Endotoxins; D014409:Tumor Necrosis Factor-alpha; D018799:Intercellular Adhesion Molecule-1; D003636:DEAE-Cellulose