Synergetic effect of dialyzer membrane and lipopolysaccharide on peripheral blood mononuclear cell cytokine production in uremic patients.
OBJECTIVE
To investigate the effect of lipopolysaccharide(LPS) and dialyzer membrane on cytokine gene expression and protein production in uremic patients on continuous ambulatory peritoneal dialysis (CAPD) and regular hemodialysis(HD).


METHODS
Interleukin-1 beta (IL-1 beta) and interleukin-1 receptor antagonist (IL-1Ra) produced by cultured peripheral blood mononuclear cells (PBMC) after exposure to cuprammonium (Cup) membrane, polysulfone (PS) membranes or endotoxin were detected using enzyme-linked immunoabsorbent assay. mRNA expression was determined simultaneously by in situ hybridization.


RESULTS
In the absence of endotoxin, a small amount of IL-1 beta and IL-1 Ra was produced by PBMC harvested from HD and CAPD patients after incubation with Cup or PS during subsequent 24-hour culture. For healthy controls, IL-1 beta was barely detectable just above the detection limit. Although no differences could be found in protein synthesis between Cup and PS, in situ hybridization showed that Cup induced markedly higher level mRNA coding for IL-1 beta and IL-1Ra. In contrast, when subsequently stimulated with endotoxin, PBMC incubated with Cup could produce significantly larger amount of IL-1 beta and IL-1Ra compared with either unstimulated cells or post-incubation PBMC with PS. LPS-stimulated PBMC in healthy subjects produced similar amount of IL-1 beta and markedly lower IL-1Ra as compared with uremic patients on HD and CAPD.


CONCLUSIONS
Two steps are required in healthy control for IL-1 beta and IL-1Ra production: induction of mRNA transcription by membrane contact, followed by LPS-induced translation, while in uremic patients on HD or CAPD bioincompatibility-membrane and LPS have a synergetic effect on IL-1 beta and IL-1Ra production. There exists an unbalance between IL-1 beta and its specific inhibitor in maintenance dialysis patients.
Gu
Y
Y
Department of Nephrology, Huashan Hospital, Shanghai Medical University, Shanghai 200040, China.
Ding
F
F
Qin
H
H
Zhao
H
H
Lin
S
S
D000328:Adult; D000368:Aged; D005260:Female; D006801:Humans; D053590:Interleukin 1 Receptor Antagonist Protein; D007375:Interleukin-1 / Q000096:biosynthesis*; D007963:Leukocytes, Mononuclear / Q000378:metabolism*; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008297:Male; D008567:Membranes, Artificial; D008875:Middle Aged; D010531:Peritoneal Dialysis, Continuous Ambulatory; D006435:Renal Dialysis; D012795:Sialoglycoproteins / Q000096:biosynthesis*; D014511:Uremia / Q000276:immunology*
C507763:IL1RN protein, human; D053590:Interleukin 1 Receptor Antagonist Protein; D007375:Interleukin-1; D008070:Lipopolysaccharides; D008567:Membranes, Artificial; D012795:Sialoglycoproteins