Metal working fluids (MWF) and microbial contaminants induce hypersensitivity pneumonitis in an experimental murine model

Abstract

Rationale Hypersensitivity pneumonitis in machinists has been attributed to the inhalation of used MWF containing contaminants. In a murine model we examined the antigenicity and inflammatory responses of MWF and microbial contaminants. Methods 6-8 wk old female Balb/c mice were sensitized intraperitoneally and intranasally with unused MWF with or without Mycobacterium immunogenum and Acinetobacter lwoffi antigen extracts. Upon completion of the study, the total serum IgE, peripheral eosinophils, and specific serum IgG1 and IgG2a antibodies were studied. Splenocytes were stimulated with antigens and supernatants assayed for cytokines by ELISA. Histological changes in the lung were also evaluated. Results Used MWF (1:20) contaminated with A. lwoffi and M immunogenum induced both cellular and antibody responses. Mice exposed to MWF and antigens extracts had lower body weights (16.4 g vs. 19.7 g; p<0.001) and peripheral eosinophilia (9.4×10 4 vs. 2.9×10 4; p<0.005) compared to normal controls. M. immunogenum-sensitized mice demonstrated higher serum specific IgG1 antibodies as compared to normal controls. A. lwoffi-sensitized mice showed increase of both IgG1 and IgG2a specific antibodies. Spleen cell proliferation was detected with A. lwoffi antigens. Lung histology demonstrated inflammatory infiltrates in the submucosa and perivascular areas. Conclusions MWF with added M. immunogenum and A. lwoffi antigens developed immune and inflammatory responses comparable to what is detected in humans.