Acute effects of hemodialysis on cytokine transcription profiles: Evidence for C-reactive protein-dependency of mediator induction

• Published in: Kidney international Vol. 70; no. 12; pp. 2124 - 2130
• Main Authors: Friedrich, B., Alexander, D., Janessa, A., Häring, H.-U., Lang, F., Risler, T.
• Format: Journal Article
• Language: English
• Published: New York, NY Elsevier Inc 01.12.2006; Nature Publishing; Elsevier Limited
• Subjects: Aged; Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy; Biological and medical sciences; C-Reactive Protein - immunology; C-Reactive Protein - metabolism; cytokines; Cytokines - genetics; Emergency and intensive care: renal failure. Dialysis management; Female; hemodialysis; Humans; Inflammation - immunology; Inflammation - prevention & control; Intensive care medicine; Kidney Failure, Chronic - immunology; Kidney Failure, Chronic - therapy; Leukocytes - physiology; Male; Medical sciences; Membrane Proteins - genetics; microarray analysis; microinflammation; Middle Aged; Nephrology. Urinary tract diseases; Oligonucleotide Array Sequence Analysis; real-time PCR; Receptors, Chemokine - genetics; Receptors, Complement - genetics; Receptors, Cytokine - genetics; Renal Dialysis - instrumentation; Renal Dialysis - methods; Reverse Transcriptase Polymerase Chain Reaction; Transcription, Genetic - immunology; hemodialysis; cytokines; microarray analysis; real-time PCR; microinflammation; Nephrology; Transcription; Hemodialysis; Induction; Acute; Cytokine; Real time; Profile; Urology; Polymerase chain reaction; Extrarenal dialysis; Acute phase protein; Mediator; Molecular biology; C reactive protein
• ISSN: 0085-2538; 1523-1755
• DOI: 10.1038/sj.ki.5001865

Chronic microinflammation increases cardiovascular morbidity in chronic hemodialysis (HD) patients. Previously published studies are controversial with respect to acute effects of HD treatment on up- or downregulation of cytokine protein levels. Twenty-nine chronic HD patients were hemodialysed for 4h with a 4008 dialyser using high-flux membranes. Patients were separated into a low (up to 1mg/dl) and a high (1.1 to 5.5mg/dl) C-reactive protein (CRP) group. Blood was drawn before HD and 240min after initiation of HD. Acute changes of transcript levels encoding pro- and anti-inflammatory mediators were analyzed in RNA stabilized immediately from blood leukocytes using microarray analysis (n=1) and quantitative real-time polymerase chain reaction (PCR) (Light Cycler) (n=29). In both patient groups, HD treatment significantly increased the transcript levels of several pro-inflammatory cytokines, such as tumor necrosis factor alpha and interleukin-8 (IL-8), and chemokine receptors such as C-X-C chemokine receptor type 4, C-C chemokine receptor type 7, and the fractakine receptor CX3C chemokine receptor 1. In the low CRP group, the increase of transcript levels for anti-inflammatory IL-1-receptor antagonist and of the receptor for the anti-inflammatory cytokines IL-10 and interferon gamma was significantly more pronounced than in the high CRP group. Subgroup analysis revealed no difference between diabetic vs non-diabetic patients. These observations point towards a marked influence of a routine hemodialysis treatment on transcription in leukocytes of pro- and anti-inflammatory cytokines and receptors relevant for microinflammation. Diminished upregulation of receptors for anti-inflammatory factors in HD patients with high CRP levels could contribute to enhanced microinflammation in those patients.