Acute effects of hemodialysis on cytokine transcription profiles: evidence for C-reactive protein-dependency of mediator induction.
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 4 h with a 4008 dialyser using high-flux membranes. Patients were separated into a low (up to 1 mg/dl) and a high (1.1 to 5.5 mg/dl) C-reactive protein (CRP) group. Blood was drawn before HD and 240 min 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.
Friedrich
B
B
Department of Medicine IV, University of Tübingen, Tübingen, Germany. bjoern.friedrich@med.uni-tuebingen.de
Alexander
D
D
Janessa
A
A
Häring
H-U
HU
Lang
F
F
Risler
T
T
D000368:Aged; D002097:C-Reactive Protein / Q000276:immunology / Q000378:metabolism*; D016207:Cytokines / Q000235:genetics*; D005260:Female; D006801:Humans; D007249:Inflammation / Q000276:immunology / Q000517:prevention & control*; D007676:Kidney Failure, Chronic / Q000276:immunology* / Q000628:therapy*; D007962:Leukocytes / Q000502:physiology; D008297:Male; D008565:Membrane Proteins / Q000235:genetics; D008875:Middle Aged; D020411:Oligonucleotide Array Sequence Analysis; D019707:Receptors, Chemokine / Q000235:genetics; D011951:Receptors, Complement / Q000235:genetics; D018121:Receptors, Cytokine / Q000235:genetics; D006435:Renal Dialysis / Q000295:instrumentation / Q000379:methods*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014158:Transcription, Genetic / Q000276:immunology
D016207:Cytokines; D008565:Membrane Proteins; D019707:Receptors, Chemokine; D011951:Receptors, Complement; D018121:Receptors, Cytokine; C085567:complement C3a receptor; D002097:C-Reactive Protein