Metal working fluid with mycobacteria and endotoxin induces hypersensitivity pneumonitis in mice

Authors: Thorne, Peter S.; Adamcakova-Dodd, Andrea; Kelly, Kevin M.; O’Neill, Marsha E.; Duchaine, Caroline
Abstract: Background: Human cases of hypersensitivity pneumonitis (HP) have been reported among machinists for over 10 yr. Although mycobacteria have been implicated as causal agents, this has not been established in experimental studies and the mechanisms remain unclear. Other constituents of in-use metalworking fluids (MWFs) may also contribute to the development of lung disease. We investigated the potential for Mycobacterium immunogenum (MI) in MWFs to induce HP. Methods: Mice were exposed intranasally for 3 wk to MI (isolated from MWFs), Saccharopolyspora rectivirgula (positive control), saline, endotoxin, MWFs spiked with endotoxin and/or MI, used MWFs, and particulate-fortified used MWFs. Responses were assessed 96 h after the last exposure. Results: Mice exposed to MI in MWFs developed lung pathology consistent with HP along with significantly more monocytes and neutrophils in lung lavage, increased CD4+/CD8+ T-lymphocyte ratio, and marked pulmonary lymphocytosis on histologic examination when compared with saline-treated control mice. Mice with Grade 2 or higher pathology (0–4 point scale) exhibited significantly elevated macrophage inflammatory protein–1a and IL-10 and a trend toward higher RANTES 96 h after the final dose. Endotoxin coexposure augmented lung pathology. Conclusion: MWFs containing mycobacteria induced granulomatous lung lesions, peribronchiolar lymphocytosis, increased cell concentrations in lavage, and up-regulation of several cytokines. These findings are consistent with HP.
Document Type: Article de recherche
Issue Date: 1 April 2006
Open Access Date: 15 November 2016
Document version: AM
This document was published in: American Journal of Respiratory and Critical Care Medicine, Vol. 173(7), 759-768 ( 2006)
American Lung Association
Alternative version: 10.1164/rccm.200405-627OC
Collection:Articles publiés dans des revues avec comité de lecture

Files in this item:
Description SizeFormat 
AJRCCM2006.pdf2.42 MBAdobe PDFThumbnail
All documents in CorpusUL are protected by Copyright Act of Canada.