TNF-alpha levels are not increased in inflamed patients carrying the CCR5 deletion 32

Background and aims: Recently we reported on a genetically predisposed protection from C-reactive protein (CRP) related mortality in dialysis patients carrying the functional CC-chemokine receptor 5 deletion 32 allele (CCR5 Delta 32) mutation. Since CCR5 Delta 32 is associated with a less pro-inflammatory immune response in mice, we hypothesized that the observed protection is (in part) due to a less pro-inflammatory cytokine profile. Methods: Cross-sectional observational study including 263 incident dialysis patients aged 18-70 years, without clinical signs of infection and/or acute vasculitis. TNF-alpha, IL-6, IL-10 and hsCRP levels were determined and studied in relation to the CCR5 genotype. Results: In the presence of elevated hsCRP, IL-6 concentration was higher irrespective of the CCR5 genotype. However, in patients with the CCR5 deletion, TNF-alpha did not differ in the presence/absence of elevated hsCRP and was not correlated with hsCRP levels in carriers of the CCR5 Delta 32 polymorphism. Conclusions: A possible underlying mechanism of the impact of CCR5 Delta 32 genotype on inflammation driven mortality in dialysis patients could be a reduced Th1 immune response as represented by decreased TNF-alpha levels. (C) 2010 Elsevier Ltd. All rights reserved.