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

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.

Occupational Silica Exposure and Pericarditis: An Uncommon Link

“…In addition, when we took an occupational history, the association of regular silica exposure helped us to think laterally. The literature reported that auto-immune diseases were also linked to silica exposure [ 11 , 12 ], and in our case, the patient has had silica exposure for several years as a sculptor. It led us to consider the previously reported associations between silica dust exposure and autoimmune disease.…”

Differential Pulmonary Toxicity and Autoantibody Formation in Genetically Distinct Mouse Strains Following Combined Exposure to Silica and Diesel Exhaust Particles

“…NOD/ShiLtJ mice and C57BL/6J mice are known to exhibit significantly distinct baseline immunophenotypic characteristics. C57BL/6J mice were included as a well-studied strain for silicosis and lung inflammation, not spontaneously developing autoimmunity nor developing autoimmune disease upon silica exposure ( 41 ). NOD/ShiLtJ mice, on the other hand, have a chronic inflammatory state, represented by high serum immunoglobulin levels compared to C57BL/6J mice ( 42 ).…”

Occupational Silica Exposure as a Potential Risk for Microscopic Polyangiitis

“…In animal experiments, the relationship between silica exposure, autoimmune diseases, and serum autoantibody positivity has been shown in many studies. 23 Proteinuria, renal immunoglobulin G, and C3 deposits were detected after exposure of lupus-prone NZM2410 mice with crystalline silica; positive markers, such as antinuclear antibody (ANA) and anti-DNA, were observed after subcutaneous administration of sodium silicate to a group of rats; 8 and silicosis exposure in mice infected with lymphocytic choriomeningitis virus has been shown to induce severe GN with elevated autoantibody levels. It has, therefore, been suggested that autoimmunity may be activated by silicosis exposure in the case of chronic viral infection as part of the pathogenesis of a prototype autoimmune disease like SLE.…”