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

Our plain-English summary of Amphibole, but not chrysotile, asbestos induces anti-nuclear autoantibodies and IL-17 in C57BL/6 mice, by A. Ferro, C.N. Zebedeo, C. Davis, et al (Journal of Immunotoxicology, 2014).

The study

• Authors: A. Ferro, C.N. Zebedeo, C. Davis, K.W. Ng, J.C. Pfau
• Journal: Journal of Immunotoxicology
• Published: 2014;11(3):283-90
• Cited by: 31 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

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.

In plain English

This was a controlled laboratory experiment in mice. Female C57BL/6 mice received two intratracheal instillations, 3 to 4 weeks apart, of a suspension of Libby amphibole asbestos ("6-Mix", containing winchite, richterite, tremolite and amosite), of intermediate chrysotile, or of saline, and were examined 8 months after the final treatment; seven saline, 10 chrysotile and 11 6-Mix mice were analysed. Positive antinuclear antibody (ANA) tests occurred in eight of 11 amphibole-exposed mice (72.7%), a significant increase over saline (p = 0.02), in which one of seven mice was positive (14.2%); two of 10 chrysotile mice were positive (20%), not significantly different from saline (p = 0.64). In amphibole-exposed mice, antibodies to Sm and Jo-1 were most frequent. Both fibers raised IL-2, IFN-gamma and IL-6 and lowered IgG1, but only amphibole raised IL-17. Suppressor B-cells rose in spleen and lungs of chrysotile mice only. The authors concluded that amphibole 6-Mix, but not chrysotile, increased the risk for autoimmunity in these mice.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: Controlled animal experiment (mouse exposure study) comparing amphibole asbestos, chrysotile and saline
• Who was studied: Wild-type female C57BL/6 mice, 6-8 weeks old at the start, raised at Idaho State University; final analysis included 7 saline, 10 chrysotile and 11 6-Mix mice, assessed 8 months after the last instillation
• Exposure: Two intratracheal instillations 3 to 4 weeks apart of 30 microlitres of a 1 mg/ml suspension (total 60 micrograms) of Libby amphibole "6-Mix" (winchite, richterite, tremolite, amosite) or of NIEHS intermediate chrysotile, or saline only
• Main results:
  • Positive ANA tests: 8 of 11 amphibole 6-Mix mice (72.7%), a significant increase versus saline (p = 0.02)
  • Saline control group: 1 of 7 mice was ANA positive (14.2%)
  • Chrysotile group: 2 of 10 mice ANA positive (20%), not significantly different from saline
  • Among ANA-positive amphibole-exposed mice, antibodies to extractable nuclear antigens Sm and Jo-1 were the most frequent
  • Serum IL-17 increased only in the amphibole 6-Mix group; IL-2, IFN-gamma and IL-6 increased with both fibers
  • IL-4 and IL-10 were not significantly elevated with either fiber; an increase in IL-10 in the 6-Mix mice was a trend only (p = 0.06)
  • Both fibers reduced serum IgG1, with no significant changes in other isotypes
  • B-suppressor cells rose significantly in spleen and lungs only in chrysotile-exposed mice; B1a B-cells in spleen rose in both fiber groups; no change in overall B- or T-cell percentages
  • Regulatory T-cells in spleen were slightly higher with chrysotile but not statistically significant (saline 3.7, 6-Mix 3.95, chrysotile 5.28 percent)
• The authors' conclusion: The authors concluded that exposure to amphibole 6-Mix, but not chrysotile, increased the risk for autoimmunity in these mice, while both fibers produced an inflammatory response
• Limitations the authors state:
  • The authors state that the study should be repeated in other mouse strains and with larger numbers of animals to clarify relevance to humans
  • The assays could not distinguish whether the antibodies were primarily to histone or dsDNA, possibly from undetected target antigen or loss of sensitivity when adapting clinical assays to mouse serum
  • Group sizes fell below the planned 12 per group because of deaths and euthanasia during the 8 months
  • Dosing was by mass, so fiber numbers and total surface area differed between the two fiber types
  • The authors state the findings require confirmation by comparing serology of chrysotile- versus amphibole-exposed human populations

Mines named here

Asbestos mines this study is about. Each mine's page says who ran it, when it worked, and what it produced.

• Libby vermiculite mine, Montana

All asbestos mines

Topics

The National Library of Medicine indexes this study under subjects our site covers: Asbestosis, Chrysotile.

Medical terms in this study, explained in our Lexicon: Amphibole Group, Chrysotile, Amphibole Asbestos, Cytokine.

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• Autoantibodies from mice exposed to Libby amphibole asbestos bind SSA/Ro52-enriched apoptotic blebs of murine macrophages — D.J. Blake, S.A. Wetzel, et al. (2008)
• Prevalence of anti-nuclear autoantibodies in subjects exposed to natural asbestiform fibers: a cross-sectional study — C. Ledda, R. Caltabiano, et al. (2018)
• Comparative health effects in mice of Libby amphibole asbestos and a fibrous amphibole from Arizona — J.C. Pfau, B. Buck, et al. (2017)
• Libby amphibole-induced mesothelial cell autoantibodies promote collagen deposition in mice — J. Gilmer, K. Serve, et al. (2016)

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