Document Detail


Reduced secretion of proinflammatory cytokines of monosodium urate crystal-stimulated monocytes in chronic renal failure: an explanation for infrequent gout episodes in chronic renal failure patients?
MedLine Citation:
PMID:  10809805     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
BACKGROUND: In gouty arthritis, monosodium urate (MSU) crystals interact with monocytes and neutrophils to produce inflammatory reactions associated with acute synovitis. In patients with end-stage renal disease (ESRD), gouty arthritis is a rare condition despite often severe hyperuricaemia. We wondered whether differences in the secretion of proinflammatory cytokines by MSU crystal-stimulated monocytes might be one explanation for the low incidence of gouty arthritis in patients with ESRD compared with healthy controls. METHODS: Thirteen patients with ESRD on intermittent haemodialysis treatment, six patients with chronic renal failure not yet on dialysis, and 15 age- and sex-matched healthy controls were examined. Monocytes, purified from peripheral blood mononuclear cells (PBMC) by immunomagnetic bead separation, were incubated for 18 h in the presence of MSU crystals, Escherichia coli lipopolysaccharide (LPS) or medium alone. The supernatants were studied for the presence of interleukin (IL)-1beta, IL-6 and tumour necrosis factor-alpha (TNF-alpha) using cytokine-specific enzyme-linked immunosorbent assays. RESULTS: Monocytes from patients with ESRD produced significantly lower amounts of IL-1beta, IL-6 and TNF-alpha after stimulation with MSU crystals or LPS than did monocytes from healthy subjects. Cytokine production was not significantly different between ESRD patients on haemodialysis and chronic renal failure patients not yet on dialysis. Artificial MSU crystals were stronger stimuli than tophus-derived 'natural' MSU crystals. CONCLUSION: We demonstrate that monocyte-associated immunosuppression in ESRD leads to reduced secretion of proinflammatory cytokines in response to stimuli such as MSU crystals. This may be one of the factors preventing many ESRD patients from the manifestation of acute gout despite often severe hyperuricaemia.
Authors:
O Schreiner; E Wandel; F Himmelsbach; P R Galle; E Märker-Hermann
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association     Volume:  15     ISSN:  0931-0509     ISO Abbreviation:  Nephrol. Dial. Transplant.     Publication Date:  2000 May 
Date Detail:
Created Date:  2000-06-14     Completed Date:  2000-06-14     Revised Date:  2004-11-17    
Medline Journal Info:
Nlm Unique ID:  8706402     Medline TA:  Nephrol Dial Transplant     Country:  ENGLAND    
Other Details:
Languages:  eng     Pagination:  644-9     Citation Subset:  IM    
Affiliation:
First Department of Medicine, University of Mainz, Mainz, Germany.
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MeSH Terms
Descriptor/Qualifier:
Adult
Aged
Aged, 80 and over
Crystallization
Cytokines / metabolism*
Cytological Techniques
Female
Gout / epidemiology*,  etiology*
Humans
Incidence
Inflammation Mediators / metabolism*
Interleukin-1 / metabolism
Interleukin-6 / metabolism
Kidney Failure, Chronic / complications,  metabolism*
Lipopolysaccharides / pharmacology
Male
Middle Aged
Tumor Necrosis Factor-alpha / metabolism
Uric Acid / pharmacology*
Chemical
Reg. No./Substance:
0/Cytokines; 0/Inflammation Mediators; 0/Interleukin-1; 0/Interleukin-6; 0/Lipopolysaccharides; 0/Tumor Necrosis Factor-alpha; 69-93-2/Uric Acid

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