Increased SOCS expression in peripheral blood mononuclear cells of end stage renal disease patients is related to inflammation and dialysis modality

Abstract

Inflammation is a characteristic of cardiovascular disease and is increased in end-stage renal disease. Suppressors of cytokine signaling (SOCS) inhibit and reflect activation of intracellular inflammatory pathways. We hypothesized that SOCS expression in peripheral blood mononuclear cells of end stage renal disease patients is increased. Whether SOCS expression in peripheral blood mononuclear cells is related to inflammation, dialysis, and dialysis modality was investigated. Monocytes and lymphocytes were isolated from peripheral blood mononuclear cells of patients not on dialysis ( n = 8), on peritoneal dialysis ( n = 8), on hemodialysis ( n = 14) and of healthy control ( n = 15) subjects. SOCS expression was assessed by real-time quantitative PCR and plasma cytokines by ELISA. In end stage renal disease patients monocyte SOCS1, and lymphocyte SOCS1 and cytokine-inducible SH2 containing protein-1 (CIS-1) gene expression were increased along with increased plasma levels of interleukin (IL)-6, tumor necrosis factor (TNF)α ,and C-reactive protein (CRP). Monocyte SOCS1 correlated with IL-6. Lymphocyte CIS-1 was increased in non-dialysis and peritoneal dialysis but not in hemodialysis patients. Lymphocyte CIS-1 in peritoneal dialysis patients correlated with plasma TNFα. Despite the relatively low number of patients studied we observed increased expression of SOCS1 in both monocytes and lymphocytes, and of CIS-1 solely in lymphocytes of the patients. SOCS expression was related to increased systemic inflammation, illustrated by a significant correlation between monocyte SOCS1 and plasma IL-6. SOCS expression in peripheral blood mononuclear cells was also affected by hemodialysis, indicated by increased lymphocyte CIS-1 in non-dialysis and peritoneal dialysis but not in hemodialysis patients. We suggest that increased SOCS expression in peripheral blood mononuclear cells of end stage renal disease patients reflects whether and to which extent systemic inflammation activates the intracellular inflammatory pathways.