title: The role of pro- and anti-inflammatory responses in silica-induced lung fibrosis.
abstract: BACKGROUND
  It has been generally well accepted that chronic inflammation is a necessary component of lung fibrosis but this concept has recently been challenged.
  
  
  METHODS
  Using biochemical, histological, immunohistochemistry, and cellular analyses, we compared the lung responses (inflammation and fibrosis) to fibrogenic silica particles (2.5 and 25 mg/g lung) in Sprague-Dawley rats and NMRI mice.
  
  
  RESULTS
  Rats treated with silica particles developed chronic and progressive inflammation accompanied by an overproduction of TNF-alpha as well as an intense lung fibrosis. Dexamethasone or pioglitazone limited the amplitude of the lung fibrotic reaction to silica in rats, supporting the paradigm that inflammation drives lung fibrosis. In striking contrast, in mice, silica induced only a limited and transient inflammation without TNF-alpha overproduction. However, mice developed lung fibrosis of a similar intensity than rats. The fibrotic response in mice was accompanied by a high expression of the anti-inflammatory and fibrotic cytokine IL-10 by silica-activated lung macrophages. In mice, IL-10 was induced only by fibrotic particles and significantly expressed in the lung of silica-sensitive but not silica-resistant strains of mice. Anti-inflammatory treatments did not control lung fibrosis in mice.
  
  
  CONCLUSIONS
  These results indicate that, beside chronic lung inflammation, a pronounced anti-inflammatory reaction may also contribute to the extension of silica-induced lung fibrosis and represents an alternative pathway leading to lung fibrosis.
authors.affiliation: Industrial Toxicology and Occupational Medicine Unit, Faculty of Medicine, Université Catholique de Louvain, Clos Chapelle-aux-champs 30.54, 1200 Brussels, Belgium. Virginie.Barbarin@toxi.ucl.ac.be
authors.forename: Virginie
authors.initials: V
authors.lastname: Barbarin
authors.forename: Aurélie
authors.initials: A
authors.lastname: Nihoul
authors.forename: Pierre
authors.initials: P
authors.lastname: Misson
authors.forename: Mohammed
authors.initials: M
authors.lastname: Arras
authors.forename: Monique
authors.initials: M
authors.lastname: Delos
authors.forename: Isabelle
authors.initials: I
authors.lastname: Leclercq
authors.forename: Dominique
authors.initials: D
authors.lastname: Lison
authors.forename: Francois
authors.initials: F
authors.lastname: Huaux
mesh_terms: D000818:Animals; D002908:Chronic Disease; D016207:Cytokines / Q000276:immunology; D005260:Female; D007155:Immunologic Factors / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D011014:Pneumonia / Q000209:etiology / Q000276:immunology* / Q000473:pathology*; D011658:Pulmonary Fibrosis / Q000209:etiology / Q000276:immunology* / Q000473:pathology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012822:Silicon Dioxide / Q000633:toxicity*
chemical_list: D016207:Cytokines; D007155:Immunologic Factors; D012822:Silicon Dioxide