Exposure to silicates and systemic autoimmune-related outcomes in rodents: a systematic review

Our plain-English summary of Exposure to silicates and systemic autoimmune-related outcomes in rodents: a systematic review, by L.M.F. Janssen, M. Ghosh, F. Lemaire, et al (Particle and Fibre Toxicology, 2022).

The study

• Authors: L.M.F. Janssen, M. Ghosh, F. Lemaire, K. Michael Pollard, P.H.M. Hoet
• Journal: Particle and Fibre Toxicology
• Published: 2022;19(1):4
• Type of article: Systematic review
• Cited by: 18 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Background: Autoimmunity can result from the interplay between genetic background and effects of environmental and/or occupational exposure to hazardous materials. Several compounds, including silica dust, have been linked with systemic autoimmunity and systemic autoimmune diseases, based on epidemiological evidence. For asbestos, a strong link with systemic autoimmune diseases does not yet exist, however, several studies have documented features of autoimmunity following asbestos exposure. Even so, human studies are limited in their ability to identify and examine isolated exposures, making it difficult to demonstrate causation or to assess pathogenic mechanisms. Therefore, this systematic review examines the existing animal evidence regarding autoimmunity and exposure to silicates (silica and asbestos).

Methods: PubMed and EMBASE were systematically searched for peer-reviewed studies examining systemic autoimmune disease-related outcomes after silicate exposure in rodents. Literature databases were searched up to September 2021 for studies written in English and where the full text was available. Search strings were established based on a PECO (Population, Exposure, Comparator, Outcome) format. After title, abstract, and full-text screening, thirty-four studies were identified for further analysis. Quality assessment through ToxR tool and qualitative analysis of the results was performed.

Results: Although there was significant heterogeneity in the included studies in terms of exposure protocol and genetic background of the rodent models used, it was noted that both genetic background and exposure to silicates [(crystalline) silica and asbestos] are highly relevant to the development of (sub-) clinical systemic autoimmune disease.

Conclusion: Parallels were observed between the findings from the animal (this review) and human (epidemiological) studies, arguing that experimental animal models are valuable tools for examining exacerbation or development of autoimmune disease after silicate exposure. However, genetic background and synergism between exposures should be considered in future studies.

© 2022. The Author(s).

In plain English

This article was a systematic review of earlier rodent experiments, not a new experiment. The authors searched PubMed and Embase for studies published before September 17, 2021 that looked for signs of systemic autoimmune disease in rodents given silica or asbestos. They included 34 studies, 23 on silica and 11 on asbestos. Most asbestos studies used Libby (six-mix) amphibole asbestos, and only two included chrysotile. In the reviewed studies, amphibole asbestos induced antinuclear antibodies (ANA) in C57BL/6 mice and was linked to proteinuria, immune complex deposition and glomerulonephritis. Chrysotile did not induce ANA, and erionite fibers did induce ANA. Crystalline silica produced a lupus-like reaction in autoimmune-prone mouse strains, but the evidence in healthy strains was less convincing. The authors rated 19 of 34 studies reliable without restrictions. The authors concluded that the evidence was more convincing for crystalline silica than for amphibole asbestos, and that chrysotile did not induce ANA or kidney malfunction. They noted that the studies used non-uniform methods and that the review protocol was not published in advance.

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: Systematic review of published rodent (animal) exposure studies, with literature searches in MEDLINE/PubMed and Embase and a quality assessment using the ToxRTool
• Who was studied: 34 included rodent studies (mice and rats): 23 on silica and 11 on asbestos
• Exposure: Silica (mostly crystalline silica such as Min-U-Sil 5, plus sodium silicate) and asbestos, mostly Libby (six-mix) amphibole asbestos (10 of 11 asbestos studies); only two asbestos studies included chrysotile. One study used erionite fibers.
• Main results:
  • In the reviewed studies, amphibole asbestos fibers, even at a low dose, induced antinuclear antibodies (ANA) in exposed C57BL/6 mice
  • Proteinuria, immune complex deposition and glomerulonephritis were reported in C57BL/6 mice after amphibole asbestos exposure
  • Chrysotile asbestos did not induce ANA in C57BL/6 mice
  • Erionite fibers also induced ANA under similar exposure conditions
  • Crystalline silica produced a lupus-like reaction (serum ANA, glomerular damage, kidney immune complex deposition) in autoimmune-prone mouse strains
  • In healthy mouse strains such as C57BL/6, the evidence for silica-induced systemic autoimmune effects was less convincing
  • Under the quality assessment, 19 of 34 studies were placed in Klimisch level 1 (reliable without restrictions)
• The authors' conclusion: The authors concluded that both amphibole asbestos and crystalline silica can induce antibodies and clinical features of systemic autoimmunity in rodents, that the evidence is more convincing for crystalline silica than for amphibole asbestos, and that chrysotile asbestos did not induce ANA or kidney malfunction
• Limitations the authors state:
  • The review protocol was not published before the review was carried out
  • The ToxR quality assessment was not done independently by the two reviewers
  • The included studies used non-uniform exposure and outcome measurements
  • The animal evidence consists mainly of observational results, which makes it hard to draw conclusions about a common pathway
  • None of the included studies used inhalation exposure
  • Chrysotile was rarely studied, and the authors said more research might be needed with these fibers

Topics

Medical terms in this study, explained in our Lexicon: Silicate, Systematic Review, Occupational Exposure, Asbestos Exposure, Causation, Crystalline.

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