title: TNF-alpha: mRNA, plasma protein levels and soluble receptors in patients on chronic hemodialysis, on CAPD and with end-stage renal failure.
abstract: BACKGROUND
  Patients on hemodialysis suffer from an impaired immunity against infectious agents, hyporesponsiveness to vaccination and are prone to develop malignancies. This clinical state of immunoincompetence may be due to a disbalance in their defense mechanisms in which TNF-alpha and its soluble receptors 1 and 2 play a central role.
  
  
  METHODS
  We measured, with double-sandwich ELISA, the levels of TNF-alpha and the soluble TNF-receptors in peripheral blood of patients on chronic intermittent hemodialysis (CIHD), on peritoneal dialysis (CAPD) and pre-dialysis end-stage renal failure (ESRF). Using reverse transcriptase polymerase chain reaction (RT-PCR) analysis, we quantified the amount of TNF-alpha mRNA in peripheral blood mononuclear cells (PBMC) obtained from these patient groups.
  
  
  RESULTS
  In none of the patient groups, elevated levels of TNF-alpha were detected with ELISA, while high levels of soluble TNF receptors were present in ESRF, CAPD and CIHD patients. This may be the result of an activated TNF-alpha system or due to their impaired renal clearance. TNF-alpha mRNA level was elevated in CIHD patients compared to ESRF and CAPD patients or healthy controls.
  
  
  CONCLUSIONS
  This suggests that only during chronic HD is the TNF-alpha system activated. High levels of sTNFR, found in ESRF or CAPD patients do not reflect activation of TNF-alpha system, but are the result of impaired renal clearance of the receptors. Indeed, we found a strong linear correlation between the levels of sTNF receptors and renal function. Nevertheless, these high levels of sTNF receptors are biological active, as they were able to bind active TNF-alpha up to 75% (range 46 - 83%) and thus inhibit the bioactivity and bioavailability of produced TNF-alpha. This may play a role in the immunoincompetence of these patients.
authors.affiliation: Department of Internal Medicine I, University Hospital, Rotterdam Dijkzigt, The Netherlands.
authors.forename: I C
authors.initials: IC
authors.lastname: van Riemsdijk-van Overbeeke
authors.forename: C C
authors.initials: CC
authors.lastname: Baan
authors.forename: C J
authors.initials: CJ
authors.lastname: Hesse
authors.forename: E H
authors.initials: EH
authors.lastname: Loonen
authors.forename: H G
authors.initials: HG
authors.lastname: Niesters
authors.forename: R
authors.initials: R
authors.lastname: Zietse
authors.forename: W
authors.initials: W
authors.lastname: Weimar
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001798:Blood Proteins / Q000032:analysis*; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods / Q000706:statistics & numerical data; D005260:Female; D006801:Humans; D007121:Immunocompetence; D007676:Kidney Failure, Chronic / Q000097:blood* / Q000276:immunology / Q000628:therapy; D008297:Male; D008875:Middle Aged; D010531:Peritoneal Dialysis, Continuous Ambulatory / Q000706:statistics & numerical data; D012333:RNA, Messenger / Q000097:blood* / Q000302:isolation & purification; D018124:Receptors, Tumor Necrosis Factor / Q000097:blood*; D006435:Renal Dialysis / Q000706:statistics & numerical data; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods / Q000706:statistics & numerical data; D012995:Solubility; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis*
chemical_list: D001798:Blood Proteins; D012333:RNA, Messenger; D018124:Receptors, Tumor Necrosis Factor; D014409:Tumor Necrosis Factor-alpha