Journal Article

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?

Oliver Schreiner, Eveline Wandel, Frido Himmelsbach, Peter R. Galle and Elisabeth Märker‐Hermann

in Nephrology Dialysis Transplantation

Published on behalf of European Renal Association - European Dialysis and Transplant Assoc

Volume 15, issue 5, pages 644-649
Published in print May 2000 | ISSN: 0931-0509
Published online May 2000 | e-ISSN: 1460-2385 | DOI: http://dx.doi.org/10.1093/ndt/15.5.644
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?

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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)‐1β, IL‐6 and tumour necrosis factor‐α (TNF‐α) using cytokine‐specific enzyme‐linked immunosorbent assays.

Results. Monocytes from patients with ESRD produced significantly lower amounts of IL‐1β, IL‐6 and TNF‐α 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.

Keywords: cytokines; end‐stage renal disease; gout; monocytes; monosodium urate crystals

Journal Article.  3710 words.  Illustrated.

Subjects: Nephrology

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