Amphibole, but not chrysotile, asbestos induces anti-nuclear autoantibodies and IL-17 in C57BL/6 mice

Abstract

Exposure to amphibole asbestos has been associated with production of autoantibodies in mice and humans, and increases the risk of systemic autoimmune disease. However, epidemiological studies of chrysotile exposure have not indicated a similar induction of autoimmune responses. To demonstrate this difference in controlled exposures in mice, and to explore possible mechanistic explanations for the difference, C57BL/6 mice were exposed intratracheally to amphibole or chrysotile asbestos, or to saline only. Serum antinuclear antibodies (ANA), antibodies to extractable nuclear antigens (ENA), serum cytokines, and immunoglobulin isotypes were evaluated 8 months after the final treatment. The percentages of lymphocyte sub-sets were determined in the spleen and lungs. The results show that amphibole, but not chrysotile, asbestos increases the frequency of ANA/ENA in mice. Amphibole and chrysotile both increased multiple serum cytokines, but only amphibole increased IL-17. Both fibers decreased IgG₁, without significant changes in other immunoglobulin isotypes. Although there were no gross changes in overall percentages of T- and B-cells in the spleen or lung, there was a significant increase in the normally rare populations of suppressor B-cells (CD19⁺, CD5⁺, CD1d⁺) in both the spleen and lungs of chrysotile-exposed mice. Overall, the results suggest that, while there may be an inflammatory response to both forms of asbestos, there is an autoimmune response in only the amphibole-exposed, but not the chrysotile-exposed mice. These data have critical implications in terms of screening and health outcomes of asbestos-exposed populations.

• Amphibole
• asbestos
• autoantibodies
• chrysotile
• inhalation toxicology
• T_H17

Acknowledgements

This work was funded in part by NIH Grant #R15 ES-21884. Core facilities at Idaho State University (Advanced Imaging and MRCF) that supported this work are funded in part by NIH Grant #P20 GM103408 (INBRE). The authors gratefully acknowledge the intellectual contributions of the Libby Epidemiology Research Program (ATSDR/CDC TS000099) team, including Curtis Noonan (PhD), University of Montana; Roger Diegel (MD), Kalispell, MT; Brad Black (MD), Libby, MT; Stephen Levin (MD), Jaime Szeinuk (MD), and Raja Flores (MD), Icahn School of Medicine at Mt Sinai, New York.