Chronic inflammation and hemodialysis reduce immune competence of peripheral blood leukocytes in end-stage renal failure patients

Immunoincompetence is a profound problem in end-stage renal failure patients undergoing hemodialysis, and chronic inflammation with altered serum levels of inflammation markers has been reported. Gene expression patterns have had little relevance for leukocyte research so far because of limitations in transcript levels and stability. Using a new stimulation system we induced the expression of immune-relevant transcripts in whole blood preparations ex vivo and stabilized transcript levels by preventing RNA degradation and uncontrolled gene induction. Using quantitative real-time PCR we could show that basal TGF-β mRNA expression is about 2-fold decreased in end-stage renal failure patients, while expression of TNF-α becomes 2-fold increased, further doubling during hemodialysis. By short term stimulation with phytohemagglutinin (PHA) for 2 h we tested for the immune competence of peripheral blood leukocytes and demonstrated that hemodialysis decreases TNF-α-mediated immune responsiveness more than 3-fold. This study shows by induction and stabilization of immune-relevant transcripts that chronic inflammation and hemodialysis are crucial factors for disturbed immune competence of end-stage renal failure patients.