title: The effect of clodronate on a mevalonate kinase deficiency cellular model.
abstract: BACKGROUND
  A potential anti-inflammatory effect of clodronate--an aminobisphosphonate--was described to antagonize the pro-inflammatory effects of the block in the mevalonate pathway, the main feature of a rare auto-inflammatory disease called mevalonate kinase deficiency (MKD).
  
  
  OBJECTIVE
  In this study we evaluated the potential anti-inflammatory effect of clodronate in MKD--a still orphan drug pediatric disease.
  
  
  METHODS
  We studied some biological parameters, nitric oxide production using Griess reagents and programmed cell death by flow cytometry, as common inflammatory parameters in MKD, in the presence of different doses of clodronate (1, 10 and 100 μM).
  
  
  RESULTS
  In our cellular model and in monocytes from patients with MKD, clodronate induced an increase in programed cell death and nitric oxide production in comparison with non-treated cells.
  
  
  CONCLUSIONS
  Our findings suggest that clodronate does not have an anti-inflammatory effect as previously reported but that it increases the epiphenomena of this pediatric disease.
authors.affiliation: Institute for Maternal and Child Health-IRCCS Burlo Garofolo, via dell'Istria 65/1, 34137 Trieste, Italy.
authors.forename: Valentina
authors.initials: V
authors.lastname: Zanin
authors.forename: Annalisa
authors.initials: A
authors.lastname: Marcuzzi
authors.forename: Elisa
authors.initials: E
authors.lastname: Piscianz
authors.forename: Josef
authors.initials: J
authors.lastname: Vuch
authors.forename: Anna Monica
authors.initials: AM
authors.lastname: Bianco
authors.forename: Lorenzo
authors.initials: L
authors.lastname: Monasta
authors.forename: Giuliana
authors.initials: G
authors.lastname: Decorti
authors.forename: Sergio
authors.initials: S
authors.lastname: Crovella
mesh_terms: D000293:Adolescent; D000328:Adult; D019386:Alendronate; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D002460:Cell Line; D002478:Cells, Cultured; D002648:Child; D004002:Clodronic Acid / Q000494:pharmacology*; D005260:Female; D006801:Humans; D007249:Inflammation / Q000139:chemically induced; D008070:Lipopolysaccharides; D008297:Male; D054078:Mevalonate Kinase Deficiency; D051379:Mice; D008954:Models, Biological; D009000:Monocytes / Q000187:drug effects*; D009569:Nitric Oxide / Q000378:metabolism; D055815:Young Adult
chemical_list: D000893:Anti-Inflammatory Agents; D008070:Lipopolysaccharides; D004002:Clodronic Acid; D009569:Nitric Oxide; D019386:Alendronate