Uremia-associated immune defect: the IL-10-CRP axis.
Unstable atherosclerotic disease is related to systemic inflammation. While this inflammation remains at a subclinical level in otherwise healthy individuals, chronic elevation of pro-inflammatory cytokines is a common feature in patients with end-stage renal disease (ESRD). Current hypotheses on the pathogenetic links between inflammation and atherosclerosis emphasize that cytokine-producing monocytes/macrophages can actively infiltrate atherosclerotic plaques. A high activation level of this cell type may contribute to plaque growth. In the healthy, some 15% to 20% of circulating monocytes may be activated for cytokine production. This percentage is much higher in dialysis patients (50%), which may contribute to the rapid progression of atherosclerosis. Anti-inflammatory mechanisms such as interleukin-10 (IL-10) limit the production of a broad range of pro-inflammatory factors. Animal models, as well as clinical findings, suggest an involvement of this cytokine in the pathogenesis of vascular lesions. In hemodialysis (HD) patients, a protective role of IL-10 against systemic inflammation could be proven. A high interindividual variability in IL-10 production leads to distinct patient groups who can or cannot effectively limit the uremia- and dialysis-induced inflammation. Single nucleotide polymorphisms (SNPs) in the promotor of the IL-10 gene may genetically explain this heterogeneity. The IL-10 genotype strongly influences the range of variation of C-reactive protein (CRP), the most widely used marker of inflammation in dialysis patients. By limiting the inflammatory activation in ESRD patients, the IL-10 genotype is predictive for the risk of cardiovascular disease, meaning that the IL-10 "high-producer" genotype is associated with a lower event rate, and even mortality, than the IL-10 "low-producer" genotype.
Girndt
Matthias
M
Medical Department IV, University of the Saarland, Homburg/Saar, Germany. matthias.girndt@uniklinik-saarland.de
Ulrich
Christof
C
Kaul
Harald
H
Sester
Urban
U
Sester
Martina
M
Köhler
Hans
H
D002097:C-Reactive Protein / Q000276:immunology*; D006801:Humans; D016753:Interleukin-10 / Q000276:immunology*; D007676:Kidney Failure, Chronic / Q000276:immunology*; D014511:Uremia / Q000276:immunology*
D016753:Interleukin-10; D002097:C-Reactive Protein