title: Uridine supplementation exerts anti-inflammatory and anti-fibrotic effects in an animal model of pulmonary fibrosis.
abstract: BACKGROUND
  Pulmonary fibrosis is a progressive disease with only few treatment options available at the moment. Recently, the nucleoside uridine has been shown to exert anti-inflammatory effects in different animal models, e.g. in acute lung injury or bronchial asthma.
  
  
  METHODS
  Therefore, we investigated the influence of uridine supplementation on inflammation and fibrosis in the classical bleomycin model. Male C57BL/6 mice received an intratracheal injection of bleomycin on day 0 and were treated intraperitoneally with uridine or vehicle. The degree of inflammation and fibrosis was assessed at different time points.
  
  
  RESULTS
  Uridine administration resulted in attenuated inflammation, as demonstrated by reduced leukocytes and pro-inflammatory cytokines in the broncho-alveolar lavage (BAL) fluid. Furthermore, collagen deposition in the lung interstitium was also reduced by uridine supplementation. Similar results were obtained in a model in which animals received repeated intraperitoneal bleomycin injections. In addition uridine inhibited collagen and TGF-ß synthesis by primary lung fibroblasts, the release of pro-inflammatory cytokines by human lung epithelial cells, as well as the production of reactive oxygen species by human neutrophils.
  
  
  CONCLUSIONS
  In summary, we were able to show that uridine has potent anti-inflammatory and anti-fibrotic properties. As uridine supplementation has been shown to be well tolerated and safe in humans, this might be a new therapeutic approach for the treatment of fibrotic lung diseases.
authors.affiliation: Department of Pneumology, University Hospital Freiburg, Killianstrasse 6, 79106, Freiburg, Germany.
authors.forename: Sanja
authors.initials: S
authors.lastname: Cicko
authors.affiliation: Department of Pneumology, University Hospital Freiburg, Killianstrasse 6, 79106, Freiburg, Germany.
authors.forename: Melanie
authors.initials: M
authors.lastname: Grimm
authors.affiliation: Department of Pneumology, University Hospital Freiburg, Killianstrasse 6, 79106, Freiburg, Germany.
authors.forename: Korcan
authors.initials: K
authors.lastname: Ayata
authors.affiliation: Department of Pneumology, University Hospital Freiburg, Killianstrasse 6, 79106, Freiburg, Germany.
authors.forename: Jessica
authors.initials: J
authors.lastname: Beckert
authors.affiliation: Department of Pneumology, University Hospital Freiburg, Killianstrasse 6, 79106, Freiburg, Germany.
authors.forename: Anja
authors.initials: A
authors.lastname: Meyer
authors.affiliation: Department of Pneumology, University Hospital Freiburg, Killianstrasse 6, 79106, Freiburg, Germany.
authors.forename: Madelon
authors.initials: M
authors.lastname: Hossfeld
authors.affiliation: Department of Pneumology, University Hospital Freiburg, Killianstrasse 6, 79106, Freiburg, Germany.
authors.forename: Gernot
authors.initials: G
authors.lastname: Zissel
authors.affiliation: Department of Pneumology, University Hospital Freiburg, Killianstrasse 6, 79106, Freiburg, Germany. marco.idzko@uniklinik-freiburg.de.
authors.forename: Marco
authors.initials: M
authors.lastname: Idzko
authors.affiliation: Department of Pneumology, University Hospital Freiburg, Killianstrasse 6, 79106, Freiburg, Germany. tobmueller@ukaachen.de.|Department of Internal Medicine I, University Hospital RWTH Aachen, Aachen, Germany. tobmueller@ukaachen.de.
authors.forename: Tobias
authors.initials: T
authors.lastname: Müller
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D001761:Bleomycin; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry; D045744:Cell Line, Tumor; D003094:Collagen / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D018836:Inflammation Mediators / Q000378:metabolism; D007962:Leukocytes / Q000187:drug effects / Q000378:metabolism; D008168:Lung / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D008297:Male; D008810:Mice, Inbred C57BL; D011014:Pneumonia / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D011658:Pulmonary Fibrosis / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D017382:Reactive Oxygen Species / Q000378:metabolism; D013997:Time Factors; D016212:Transforming Growth Factor beta / Q000378:metabolism; D014529:Uridine / Q000494:pharmacology*
chemical_list: D000893:Anti-Inflammatory Agents; D016207:Cytokines; D018836:Inflammation Mediators; D017382:Reactive Oxygen Species; D016212:Transforming Growth Factor beta; D001761:Bleomycin; D003094:Collagen; D014529:Uridine