Characterization of the innate immune response to chronic aspiration in a novel rodent model.

Published online

Journal Article

BACKGROUND: Although chronic aspiration has been associated with several pulmonary diseases, the inflammatory response has not been characterized. A novel rodent model of chronic aspiration was therefore developed in order to investigate the resulting innate immune response in the lung. METHODS: Gastric fluid or normal saline was instilled into the left lung of rats (n = 48) weekly for 4, 8, 12, or 16 weeks (n = 6 each group). Thereafter, bronchoalveolar lavage specimens were collected and cellular phenotypes and cytokine concentrations of IL-1alpha, IL-1beta, IL-2, IL-4, IL-6, IL-10, GM-CSF, IFN-gamma, TNF-alpha, and TGF-beta were determined. RESULTS: Following the administration of gastric fluid but not normal saline, histologic specimens exhibited prominent evidence of giant cells, fibrosis, lymphocytic bronchiolitis, and obliterative bronchiolitis. Bronchoalveolar lavage specimens from the left (treated) lungs exhibited consistently higher macrophages and T cells with an increased CD4:CD8 T cell ratio after treatment with gastric fluid compared to normal saline. The concentrations of IL-1alpha, IL-1beta, IL-2, TNF-alpha and TGF-beta were increased in bronchoalveolar lavage specimens following gastric fluid aspiration compared to normal saline. CONCLUSION: This represents the first description of the pulmonary inflammatory response that results from chronic aspiration. Repetitive aspiration events can initiate an inflammatory response consisting of macrophages and T cells that is associated with increased TGF-beta, TNF-alpha, IL-1alpha, IL-1beta, IL-2 and fibrosis in the lung. Combined with the observation of gastric fluid-induced lymphocyitic bronchiolitis and obliterative bronchiolitis, these findings further support an association between chronic aspiration and pulmonary diseases, such as obliterative bronchiolitis, pulmonary fibrosis, and asthma.

Full Text

Duke Authors

Cited Authors

  • Appel, JZ; Lee, SM; Hartwig, MG; Li, B; Hsieh, C-C; Cantu, E; Yoon, Y; Lin, SS; Parker, W; Davis, RD

Published Date

  • November 27, 2007

Published In

Volume / Issue

  • 8 /

Start / End Page

  • 87 -

PubMed ID

  • 18042282

Electronic International Standard Serial Number (EISSN)

  • 1465-993X

Digital Object Identifier (DOI)

  • 10.1186/1465-9921-8-87

Language

  • eng

Conference Location

  • England