title: Production of monokines in patients under polysulphone haemodiafiltration is influenced by the ultrafiltration flow rate.
abstract: BACKGROUND
  Chronic haemodialysis patients show various clinical signs of immunodeficiency and there is growing evidence that a dysregulated monocyte cytokine production is heavily involved in this deficiency. The production of monokines in vitro has been proposed to correlate closely with the in vivo immune status and to be of high clinical relevance in cuprophane haemodialysis. Even though it is well known that the biocompatibility of dialyser membranes has a significant impact on immune functions, little is known about the influence of the ultrafiltration flow rate (UFR). The aim of this study was to investigate the potential long-term effects of UFR on the production of interleukin-10 (IL-10), interleukin-1beta (IL-1beta) and interleukin-6 (IL-6) in an intra-individual study design.
  
  
  METHODS
  In 11 patients previously treated with polysulphone haemodiafiltration, UFR was reduced from 40-46 ml/min to 24-28 ml/min, then to 7-10 ml/min before it was reinstated at 40-46 ml/min for periods of 4 weeks each. Monokine secretion into culture supernatants and mRNA expression (assessed using a novel Taqman PCR technique), were determined in a whole blood assay after lipopolysaccharide stimulation.
  
  
  RESULTS
  Reduction of UFR led to a significant increase in IL-10 secretion and mRNA expression (P=0.012, P=0.001). Conversely, a substantial (but not complete) decrease was observed when UFR returned to initial levels. In contrast, supernatant concentrations of IL-1beta (P=0.04) and IL-6 (P=0.003), and mRNA expression of both monokines (P<0.001, P<0.001) decreased significantly when UFR was reduced. Calculation of the IL-1beta/IL-10 ratio also revealed a decrease when UFR was reduced, with an increase again being observed when the initial degree of UFR was reinstated (P<0.001).
  
  
  CONCLUSIONS
  These results indicate a significant impact of UFR on the production of monokines at both the transcriptional and the protein level. We suggest that middle molecule removal has to be considered as a possible pathophysiological mechanism to explain our findings. Since monokine production in vitro was shown to be closely correlated with the in vivo immune status in patients on cuprophane haemodialysis, further investigations are necessary to clarify the impact of UFR on the immunocompetence of patients under polysulphone haemodiafiltration.
authors.affiliation: Institute of Immunology and Transfusion Medicine, University of Lübeck School of Medicine, Ratzeburger Allee 160, D-23538 Lübeck, Germany.
authors.forename: M
authors.initials: M
authors.lastname: Müller-Steinhardt
authors.forename: N
authors.initials: N
authors.lastname: Kock
authors.forename: C
authors.initials: C
authors.lastname: Härtel
authors.forename: H
authors.initials: H
authors.lastname: Kirchner
authors.forename: J
authors.initials: J
authors.lastname: Steinhoff
mesh_terms: D000328:Adult; D000368:Aged; D001672:Biocompatible Materials; D001772:Blood Cell Count; D002097:C-Reactive Protein / Q000032:analysis; D005260:Female; D017583:Hemodiafiltration; D006440:Hemofiltration; D006801:Humans; D007378:Interleukins / Q000097:blood / Q000235:genetics; D007676:Kidney Failure, Chronic / Q000097:blood* / Q000628:therapy*; D008297:Male; D008567:Membranes, Artificial; D008875:Middle Aged; D015846:Monokines / Q000096:biosynthesis*; D011108:Polymers; D012333:RNA, Messenger / Q000097:blood; D012039:Regional Blood Flow; D013450:Sulfones; D014508:Urea / Q000097:blood; D001613:beta 2-Microglobulin / Q000097:blood
chemical_list: D001672:Biocompatible Materials; D007378:Interleukins; D008567:Membranes, Artificial; D015846:Monokines; D011108:Polymers; D012333:RNA, Messenger; D013450:Sulfones; D001613:beta 2-Microglobulin; C017662:polysulfone P 1700; D014508:Urea; D002097:C-Reactive Protein