Animal models of rheumatoid arthritis‐associated interstitial lung disease

Abstract

Background Rheumatoid arthritis‐associated interstitial lung disease (RA‐ILD) is an irreversible pathologic condition of unknown cause, commonly involving the joint and the lung with variable amounts of fibrotic change. In contrast to rheumatoid arthritis or other chronic interstitial lung diseases such as interstitial pulmonary fibrosis, there is so far no extensively accepted or implemented animal model for this disease. Aims To provide guidance for those who are investigating the pathogenesis of RA‐ILD with animal models. Materials and Methods An analysis of papers from PubMed during 1978‐2020. Results We outline the present status quo for animal models of RA‐ILD about their modeling methods and pathogenesis, compare their pros and cons with respect to their ability to mimic the clinical and histological features of human disease and discuss their applicability for future research. Discussion There is no doubt that these animal models do provide valuable information relating to the pathogenesis of RA‐ILD and the development of effective therapeutic drugs. Nevertheless, these animal models can not entirely recapitulate clinical pathology and have some limitations in experimental research application. Therefore, it should be emphasized that we should improve and explore animal models in more accordance with the pathogenesis and clinical characteristics of human RA‐ILD. Conclusion These established animal models of the disease can significantly progress our understanding of the etiology of RA‐ILD, the fundamental mechanisms of its pathogenesis and the identification of new bio‐markers, and can contribute to the development and implementation of novel treatment strategies.

Rheumatoid arthritis-interstitial lung disease: manifestations and current concepts in pathogenesis and management

“…Lung tissue from RA-ILD patients contains greater numbers of inducible bronchial-associated lymphoid tissue than IPF patients, suggesting that immune dysregulation may play a more central role in RA-ILD than IPF [87]. Understanding RA-ILD pathogenesis via animal models Acknowledging that there are currently no widely accepted animal models for RA-ILD, the most commonly employed methods used to generate animal models in RA-ILD include induction via immune stimulants or through genetic engineering via gene mutation or transgenic systems [88]. Though there are multiple models of RA designed to replicate joint pathology, there are currently only three main arthritic models which contain lung pathology: the SKG murine model; the adjuvant arthritis model; and the tumour necrosis factor (TNF)-transgenic model [89].…”

Fibrinogen-Like Protein 1 Serves as an Anti-Inflammatory Agent for Collagen-Induced Arthritis Therapy in Mice

“…In contrast, the cellular infiltration of lung was observed in normal saline- and Fgl1-treated CIA mouse model as compared with normal DBA/1J mice ( Figure 6C ). It may cause by the anti‐citrullinated protein antibodies (ACPAs) can interact with various citrullinated proteins that not only be generated at joints, but also in the lung, thereby inducing RA‐associated lung inflammation ( 20 , 21 ). Collectively, these results indicate that Fgl1 treatment may not cause obvious toxicity to normal organs.…”

Resveratrol Ameliorates Fibrosis in Rheumatoid Arthritis-Associated Interstitial Lung Disease via the Autophagy–Lysosome Pathway

“…We used the previous modeling method of chicken type II collagen and complete Freund’s adjuvant combined with bleomycin [ 30 , 34 ]. CIA mice were induced by both CFA and Col II.…”