Metalworking Fluid with Mycobacteria and Endotoxin Induces Hypersensitivity Pneumonitis in Mice

Peter S Thorne; Andrea Adamcakova-Dodd; Kevin M Kelly; Marsha E O'Neill; Caroline Duchaine

doi:10.1164/rccm.200405-627OC

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Metalworking Fluid with Mycobacteria and Endotoxin Induces Hypersensitivity Pneumonitis in Mice

Journal article

Open access

Peer reviewed

Metalworking Fluid with Mycobacteria and Endotoxin Induces Hypersensitivity Pneumonitis in Mice

Peter S Thorne, Andrea Adamcakova-Dodd, Kevin M Kelly, Marsha E O'Neill and Caroline Duchaine

American journal of respiratory and critical care medicine, Vol.173(7), pp.759-768

12/30/2005

DOI: 10.1164/rccm.200405-627OC

PMCID: PMC2662953

PMID: 16387809

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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–1α 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.

C. Environmental and Occupational Lung Disease

endotoxin

hypersensitivity pneumonitis

metalworking fluids

mycobacteria

Saccharopolyspora rectivirgula

Details

Title: Subtitle: Metalworking Fluid with Mycobacteria and Endotoxin Induces Hypersensitivity Pneumonitis in Mice
Creators: Peter S Thorne - University of Iowa, Occupational and Environmental Health
Andrea Adamcakova-Dodd - University of Iowa, Occupational and Environmental Health
Kevin M Kelly - University of Iowa, Anthropology
Marsha E O'Neill
Caroline Duchaine
Resource Type: Journal article
Publication Details: American journal of respiratory and critical care medicine, Vol.173(7), pp.759-768
DOI: 10.1164/rccm.200405-627OC
PMID: 16387809
PMCID: PMC2662953
NLM abbreviation: Am J Respir Crit Care Med
ISSN: 1073-449X
eISSN: 1535-4970
Publisher: American Thoracic Society
Language: English
Date published: 12/30/2005
Academic Unit: Anthropology; Civil and Environmental Engineering; Occupational and Environmental Health; Stead Family Department of Pediatrics
Record Identifier: 9983557432102771

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