title: Pulmonary delivery of docosahexaenoic acid mitigates bleomycin-induced pulmonary fibrosis.
abstract: BACKGROUND
  Pulmonary fibrosis is an untreatable, fatal disease characterized by excess deposition of extracellular matrix and inflammation. Although the etiology of pulmonary fibrosis is unknown, recent studies have implicated dysregulated immune responses and wound healing. Since n-3 polyunsaturated fatty acids (n-3 PUFAs) may beneficially modulate immune responses in a variety of inflammatory disorders, we investigated the therapeutic role of docosahexaenoic acid (DHA), a single n-3 PUFA, in lung fibrosis.
  
  
  METHODS
  Intratracheal DHA or PBS was administered to mouse lungs 4 days prior to intratracheal bleomycin treatment. Body weight and survival were monitored for 21 days. Bronchoalveolar fluid (BALF) and lung inflammatory cells, cytokines, eicosanoids, histology and lung function were determined on serial days (0, 3, 7, 14, 21) after bleomycin injury.
  
  
  RESULTS
  Intratracheal administration of DHA mitigated bleomycin-induced lung injury. Mice pretreated with DHA had significantly less weight loss and mortality after bleomycin injury. The lungs from DHA-pretreated mice had markedly less fibrosis. DHA pretreatment also protected the mice from the functional changes associated with bleomycin injury. Bleomycin-induced cellular inflammation in BALF and lung tissue was blunted by DHA pretreatment. These advantageous effects of DHA pretreatment were associated with decreased IL-6, LTB4, PGE2 and increased IL-10.
  
  
  CONCLUSIONS
  Our findings demonstrate that intratracheal administration of DHA, a single PUFA, protected mice from the development of bleomycin-induced pulmonary inflammation and fibrosis. These results suggest that further investigations regarding the role of n-3 polyunsaturated fatty acids in fibrotic lung injury and repair are needed.
authors.forename: Hongyun
authors.initials: H
authors.lastname: Zhao
authors.forename: Yee
authors.initials: Y
authors.lastname: Chan-Li
authors.forename: Samuel L
authors.initials: SL
authors.lastname: Collins
authors.forename: Yuan
authors.initials: Y
authors.lastname: Zhang
authors.forename: Robert W
authors.initials: RW
authors.lastname: Hallowell
authors.forename: Wayne
authors.initials: W
authors.lastname: Mitzner
authors.affiliation: Department of Medicine, Johns Hopkins University School of Medicine, 1830 East Monument Street, 5th floor, Baltimore, MD, USA. mhorton2@jhmi.edu.
authors.forename: Maureen R
authors.initials: MR
authors.lastname: Horton
mesh_terms: D000818:Animals; D001761:Bleomycin / Q000008:administration & dosage; D004281:Docosahexaenoic Acids / Q000627:therapeutic use*; D005260:Female; D051379:Mice; D008810:Mice, Inbred C57BL; D011658:Pulmonary Fibrosis / Q000139:chemically induced / Q000188:drug therapy*; D014132:Trachea
chemical_list: D001761:Bleomycin; D004281:Docosahexaenoic Acids
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