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?

Background. In gouty arthritis, monosodium urate (MSU) crystals interact wi th monocytes and neutrophils to produce inflammatory reactions associated w ith acute synovitis. In patients with end-stage renal disease (ESRD), gouty arthritis is a rare condition despite often severe hyperuricaemia. We wond ered whether differences in the secretion of proinflammatory cytokines by M SU crystal-stimulated monocytes might be one explanation for the low incide nce of gouty arthritis in patients with ESRD compared with healthy controls . Methods. Thirteen patients with ESRD on intermittent haemodialysis treatmen t, six patients with chronic renal failure not yet on dialysis, and 15 age- and sex-matched healthy controls were examined. Monocytes, purified from p eripheral 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)-1 beta, IL-6 and tumour necrosis factor-a lpha (TNF-alpha) using cytokine-specific enzyme-linked immunosorbent assays . Results. Monocytes from patients with ESRD produced significantly lower amo unts of IL-1 beta, IL-6 and TNF-alpha after stimulation with MSU crystals o r 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 s tronger stimuli than tophus-derived 'natural' MSU crystals. Conclusion. We demonstrate that monocyte-associated immunosuppression in ES RD leads to reduced secretion of proinflammatory cytokines in response to s timuli such as MSU crystals. This may be one of the factors preventing many ESRD patients from the manifestation of acute gout despite often severe hy peruricaemia.