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Metalworking fluid with mycobacteria and endotoxin induces hypersensitivity pneumonitis in mice
Peter S Thorne1, Andrea Adamcakova-Dodd, Kevin M Kelly
1The University of Iowa, College of Public Health, 100 Oakdale Campus, IREH Iowa City, IA 52242-5000, USA. peter-thorne@uiowa.edu
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.
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.
Insights
Mycobacterium immunogenum in metalworking fluids causes hypersensitivity pneumonitis (HP) in mice. This study confirms mycobacteria as a cause of HP in machinists, highlighting fluid contaminants as lung disease triggers.
Area of Science:
- Occupational Health
- Immunology
- Environmental Health
Background:
- Hypersensitivity pneumonitis (HP) is linked to machinist exposure to metalworking fluids (MWFs).
- Mycobacteria are suspected causes of HP, but experimental evidence and mechanisms are lacking.
- Other MWF components may also contribute to lung disease.
Purpose of the Study:
- To investigate the potential of Mycobacterium immunogenum (MI) in MWFs to induce HP in a mouse model.
- To elucidate the role of MI and co-exposures in MWF-induced lung pathology.
Main Methods:
- Mice were intranasally exposed to MI, controls, or various MWF formulations for 3 weeks.
- Lung responses, including cellularity and cytokine levels, were assessed post-exposure.
- Histopathology and immune cell profiles were analyzed.
Main Results:
- MI exposure in MWFs induced lung pathology consistent with HP.
- Increased monocytes, neutrophils, and a higher CD4+/CD8+ T-lymphocyte ratio were observed in lung lavage.
- Elevated inflammatory markers (MIP-1α, IL-10) and lymphocytosis were noted, with endotoxin co-exposure exacerbating pathology.
Conclusions:
- Metalworking fluids containing mycobacteria can induce granulomatous lung lesions and immune responses characteristic of HP.
- These findings support mycobacteria as a causative agent in MWF-related HP.
- The study provides experimental evidence for HP induction by MWF contaminants.
