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 1mg/dl) and a high (1.1 to 5.5mg/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.