Nephrology Dialysis Transplantation, Vol 13, Issue 6 1458-1464, Copyright © 1998 by Oxford University Press
C Tetta, J Cavaillon, M Schulze, C Ronco, P Ghezzi, G Camussi, A Serra, F Curti and G Lonnemann
Background: Sepsis is associated with enhanced
cytokine production. Here, we examined the in vitro
removal of plasma cytokines during continuous plasma filtration coupled
with sorbent adsorption. Methods: Proinflammatory
(tumour necrosis factor-&agr;, interleukins-1, -8) and
anti-inflammatory (interleukin 1 receptor antagonist, soluble tumour
necrosis factor receptor type I and II) cytokines in whole blood spiked
with Escherichia coli endotoxin were determined during
2-h recirculation in the ultrafiltrate (condition A), plasma filtrate
(condition B), before and after different sorbents (of the
AmberliteR-, AmberchromeR-
AmbersorbR-type and charcoal). We studied the
maximal adsorbing capacity, the 1% leakage test for cytokines and C3a des
Arg and the adsorption of complement-dependent leukocyte chemiluminescence.
Plasma proteins eluted from the resins were examined by sodium dodecyl
sulphate polyacrylamide gel electrophoresis and immunoblotting with an
anti-human &agr;2-macroglobulin. Results: In
condition B, we observed a 40- and 121-fold % increase
(vs condition A) in the removal mass and clearance of
tumour necrosis factor-&agr;. For all other cytokines, the removed mass
and the clearance increased from 2.3- up to 6-fold. The
AmberchromeR but not the
AmberliteR or AmbersorbR
resins could remove the highest amount of cytokines and could reduce
complement-dependent chemiluminescence. Two protein bands of approximately
400 000 D and 200 000 D were eluted only from
AmberchromeR resins and immunoprecipitated by
anti-human &agr;2-macroglobulin and anti-human C3c antibodies,
respectively. Conclusions: These studies suggest an
efficient removal of cytokines in continuous plasma filtration with sorbent
adsorption. The binding of &agr;2-macroglobulin, a carrier of cytokines
in plasma, might be an additional mechanism in the removal of cytokines
from plasma. Key words: cytokines; resins;
haemofiltration; plasma filtration; plasmapheresis; sepsis
ORIGINAL ARTICLES
Removal of cytokines and activated complement components in an experimental model of continuous plasma filtration coupled with sorbent adsorption
Clinical and Laboratory Research Department, Bellco S. p. A., Via Camurana 1/A, I-41037 Mirandola (Mo), Italy; Nephrology, University of Pavia at Varese, Italy; Laboratory of Immunopathology, University of Turin, Italy; Blood Bank, G Strumia, Molinette Hospital, Turin, Italy; Unité d'Immunoallergie, Institut Pasteur, Paris, France; Department of Nephrology, S Bortolo Hospital, Vicenza, Italy; Department of Nephrology, S Croce and Carle Hospital, Cuneo, Italy; Department of Nephrology, Hannover School of Medicine, Hannover, Germany; Corresponding author
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