title: Dissociation between beta-2 microglobulin and IL-1 production in hemodialyzed patients.
abstract: BACKGROUND
  beta-2 microglobulin is predominant in amyloid deposits in patients undergoing long term hemodialysis. Amyloid accumulation has been ascribed to dialysis membranes, endotoxin contamination of the dialysate, uremia and chronic systemic inflammation associated with enhanced monocytic cytokine production in hemodialyzed patients. Interleukin-1 has been proposed to play a critical role in the induction of beta-2 microglobulin synthesis and release.
  
  
  METHODS
  We examined if monocytes contribute to beta-2 microglobulin production upon stimulation with inflammatory mediators that are generated during hemodialysis and investigated the production of beta-2 microglobulin by cells from patients, with and without clinical signs of amyloidosis, at the time when patients' monocytes contained maximal intracellular accumulation of IL-1.
  
  
  RESULTS
  We demonstrated that only monocytes are able to release increased levels of beta-2 microglobulin upon stimulation by IL-1, TNF alpha, C5a and LPS. Increased levels of beta-2 microglobulin were associated with increased levels of beta-2 microglobulin mRNA. Before dialysis session, 20-60% of circulating CD14+ monocytes from patients contained IL-1. At the time when maximal IL-1 production was detected, we showed by RT-PCR increased transcription of IL-1 gene in patients' monocytes. We observed that monocytes from patients with amyloidosis contained higher amounts of IL-1 as compared to monocytes from patients without clinical signs of amyloidosis, but could not secrete increased amounts of beta-2 microglobulin upon LPS-stimulation.
  
  
  CONCLUSIONS
  Our data indicated that chronic inflammation, as demonstrated by increased intracellular IL-1 expression, is not associated with increased production of beta-2 microglobulin by monocytes from patients on hemodialysis.
authors.affiliation: INSERM U430, Paris, France.
authors.forename: M P
authors.initials: MP
authors.lastname: Carreno
authors.forename: Y
authors.initials: Y
authors.lastname: Rousseau
authors.forename: J L
authors.initials: JL
authors.lastname: Poignet
authors.forename: G
authors.initials: G
authors.lastname: Jahns
authors.forename: B
authors.initials: B
authors.lastname: Cholley
authors.forename: M D
authors.initials: MD
authors.lastname: Kazatchkine
authors.forename: N
authors.initials: N
authors.lastname: Haeffner-Cavaillon
mesh_terms: D000293:Adolescent; D000328:Adult; D000686:Amyloidosis / Q000378:metabolism; D006801:Humans; D007375:Interleukin-1 / Q000096:biosynthesis*; D008070:Lipopolysaccharides / Q000494:pharmacology; D008875:Middle Aged; D009000:Monocytes / Q000378:metabolism; D006435:Renal Dialysis; D001613:beta 2-Microglobulin / Q000096:biosynthesis*
chemical_list: D007375:Interleukin-1; D008070:Lipopolysaccharides; D001613:beta 2-Microglobulin