Cytokines and growth factors in mostly atherosclerotic patients on hemodialysis determined by biochip array technology.
BACKGROUND
The lifespan of patients with chronic renal failure (CRF) is reduced, and coronary artery disease is the leading cause of morbidity and mortality in these patients. The progression of atherosclerosis is accelerated and angiogenesis is impaired in CRF. Risk factors that could contribute to further understanding of vascular pathology include markers of inflammation and growth factors. The purpose of this study was to determine the levels of cytokines (IL-2, IL4, IL-6, IL-8, IL-10, IL-1 alpha, IL-1 beta), vascular endothelial growth factor (VEGF), epidermal growth factor (EGF), interferon-gamma (IFN gamma), tumor necrosis factor-alpha (TNFalpha) and monocyte chemotactic protein-1 (MCP-1) in patients on chronic hemodialysis (HD; n=75), and to compare values with those of control subjects (n=113).


METHODS
Evidence((R)) biochip array analyzer was used for quantification of plasma concentrations in samples.


RESULTS
Significant differences were found between the control subjects and HD patients. IL-2 (p<0.001), IL-4 (p<0.001) and EGF (p<0.001) levels were higher in controls than in HD patients, while IL-6 (p<0.001), IL-8 (p=0.081), IL-10 (p=0.008), TNFalpha (p<0.001), IL-1 beta (p<0.001) and MCP-1 (p<0.001) levels were higher in HD patients. We also found IL-2 (p=0.015) and IL-1 alpha (p=0.035) levels to be significantly higher in males than females, while IL-4 (p=0.025) and IL-1 beta (p=0.049) levels were significantly higher in females. Among HD patients, IL-2 levels were higher in patients under the age of 50 years (p<0.048). It was also higher in female than in male patients (p<0.035) and in patients on HD for more than 10 years (p<0.009). IL-6 levels were higher in patients over the age of 50 years (p<0.047). Patients with previous glomerulonephritis had the highest level of IL-6 compared to patients with previous pyelonephritis and diabetes mellitus (p<0.063). IL-6 levels were higher in patients with concomitant hepatitis C virus (HCV) infection (p<0.036) and in patients with developed atherosclerosis (p<0.003). IL-8 levels were higher in patients over the age of 50 years (p<0.003) and in the group with previous glomerulonephritis (p<0.031). IL-10 levels were higher in the group with developed atherosclerosis (p<0.045). EGF was the highest in the group of patients with previous diabetes mellitus compared to pyelonephritis and glomerulonephritis groups (p<0.073). TNFalpha levels were higher in the patient population on HD for more than 10 years (p<0.032) and in the concomitant HCV group (p<0.073). IL-1 beta levels were higher in the HCV group (p<0.088).


CONCLUSIONS
Plasma concentrations of some cytokines and growth factors could serve as useful diagnostic and prognostic parameters for patients with CRF on HD.
Sertic
Jadranka
J
Department of Clinical Chemistry, Zagreb University School of Medicine, Zagreb, Croatia. jadranka.sertic@kbc-zagreb.hr
Slavicek
Jasna
J
Bozina
Nada
N
Malenica
Branko
B
Kes
Petar
P
Reiner
Zeljko
Z
D050197:Atherosclerosis / Q000097:blood* / Q000473:pathology; D015415:Biomarkers / Q000097:blood; D016022:Case-Control Studies; D018932:Chemokine CCL2 / Q000097:blood; D016207:Cytokines / Q000097:blood*; D018450:Disease Progression; D004815:Epidermal Growth Factor / Q000097:blood*; D005260:Female; D006801:Humans; D007371:Interferon-gamma / Q000097:blood; D008297:Male; D008875:Middle Aged; D040081:Protein Array Analysis / Q000379:methods*; D012016:Reference Values; D006435:Renal Dialysis; D014409:Tumor Necrosis Factor-alpha / Q000097:blood; D042461:Vascular Endothelial Growth Factor A / Q000097:blood*
D015415:Biomarkers; D018932:Chemokine CCL2; D016207:Cytokines; D014409:Tumor Necrosis Factor-alpha; D042461:Vascular Endothelial Growth Factor A; D004815:Epidermal Growth Factor; D007371:Interferon-gamma