title: Increased expression of SOCS3 in monocytes and SOCS1 in lymphocytes correlates with progressive loss of renal function and cardiovascular risk factors in chronic kidney disease.
abstract: Inflammation, an independent cardiovascular disease risk factor is common in patients with chronic kidney disease. Suppressors of cytokine signaling (SOCS) are induced by cytokines in a variety of cells and modulate inflammatory responses. We hypothesized that in chronic kidney disease, SOCS expression in peripheral blood mononuclear cells is increased, and related to inflammation and renal function. We also tested correlations between SOCS expression and biomarkers and risk factors of cardiovascular disease. Whether monocytes and lymphocytes differentially respond to interleukin-6 (IL-6) was tested ex vivo. Monocytes and lymphocytes were isolated from peripheral blood of chronic kidney disease patients (n=9) and controls (n=11). In three other healthy subjects, whole blood was incubated with IL-6 before cell isolation. SOCS expression was assessed by real-time quantitative PCR. Plasma cytokines were measured as well as pulse wave velocity. SOCS3 expression was increased in monocytes and SOCS1 in lymphocytes along with increased plasma levels of IL-6 and tumor necrosis factor-alpha (TNFalpha) in chronic kidney disease patients. While monocyte SOCS3 correlated with glomerular filtration rate, urea and diastolic blood pressure, lymphocyte SOCS1 correlated with TNFalpha, pulse wave velocity and systolic blood pressure. IL-6 stimulation of whole blood caused expression of different SOCS genes in monocytes and lymphocytes. Increased expression of SOCS3 in monocytes versus SOCS1 in lymphocytes coincided with elevated plasma levels of IL-6 and TNFalpha, suggesting that these cell types process the uremic milieu differently. This could reflect cell-specific responses to inflammation, as supported by our ex vivo study. Moreover, increased SOCS expression in peripheral blood mononuclear cells correlated with decreased renal function. Since chronic kidney disease predisposes to cardiovascular disease, we speculate that increased SOCS expression in peripheral blood mononuclear cells could be a new marker of cardiovascular disease in chronic kidney disease patients.
authors.affiliation: Department of Nephrology and Hypertension, University Medical Center Utrecht, The Netherlands.
authors.forename: M Mehdi
authors.initials: MM
authors.lastname: Rastmanesh
authors.forename: Hans A R
authors.initials: HA
authors.lastname: Bluyssen
authors.forename: Jaap A
authors.initials: JA
authors.lastname: Joles
authors.forename: Peter
authors.initials: P
authors.lastname: Boer
authors.forename: Nel
authors.initials: N
authors.lastname: Willekes
authors.forename: Branko
authors.initials: B
authors.lastname: Braam
mesh_terms: D000368:Aged; D015415:Biomarkers; D001794:Blood Pressure / Q000502:physiology; D002318:Cardiovascular Diseases / Q000453:epidemiology / Q000378:metabolism*; D016207:Cytokines / Q000097:blood; D018450:Disease Progression; D005260:Female; D005919:Glomerular Filtration Rate; D006801:Humans; D015850:Interleukin-6 / Q000494:pharmacology; D007676:Kidney Failure, Chronic / Q000150:complications / Q000378:metabolism* / Q000473:pathology*; D007677:Kidney Function Tests; D008214:Lymphocytes / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012307:Risk Factors; D000071222:Suppressor of Cytokine Signaling 1 Protein; D000071223:Suppressor of Cytokine Signaling 3 Protein; D050826:Suppressor of Cytokine Signaling Proteins / Q000096:biosynthesis* / Q000235:genetics
chemical_list: D015415:Biomarkers; D016207:Cytokines; D015850:Interleukin-6; C108944:SOCS1 protein, human; C106644:SOCS3 protein, human; D000071222:Suppressor of Cytokine Signaling 1 Protein; D000071223:Suppressor of Cytokine Signaling 3 Protein; D050826:Suppressor of Cytokine Signaling Proteins