title: Metalworking fluid with mycobacteria and endotoxin induces hypersensitivity pneumonitis in mice.
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-1alpha and IL-10 and a trend toward higher RANTES 96 h after the final dose. Endotoxin coexposure augmented lung pathology.
  
  
  CONCLUSIONS
  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.
authors.affiliation: The University of Iowa, College of Public Health, 100 Oakdale Campus, IREH Iowa City, IA 52242-5000, USA. peter-thorne@uiowa.edu
authors.forename: Peter S
authors.initials: PS
authors.lastname: Thorne
authors.forename: Andrea
authors.initials: A
authors.lastname: Adamcakova-Dodd
authors.forename: Kevin M
authors.initials: KM
authors.lastname: Kelly
authors.forename: Marsha E
authors.initials: ME
authors.lastname: O'neill
authors.forename: Caroline
authors.initials: C
authors.lastname: Duchaine
mesh_terms: D000336:Aerosols; D000393:Air Pollutants / Q000633:toxicity*; D000542:Alveolitis, Extrinsic Allergic / Q000209:etiology* / Q000276:immunology / Q000378:metabolism; D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology / Q000276:immunology; D016516:CD4-CD8 Ratio; D004195:Disease Models, Animal; D004731:Endotoxins / Q000633:toxicity*; D005260:Female; D019570:Inhalation Exposure / Q000009:adverse effects*; D008168:Lung / Q000473:pathology; D008669:Metallurgy; D051379:Mice; D008810:Mice, Inbred C57BL; D009161:Mycobacterium / Q000472:pathogenicity*; D013601:T-Lymphocytes / Q000276:immunology / Q000473:pathology
chemical_list: D000336:Aerosols; D000393:Air Pollutants; D004731:Endotoxins