Establishment of a Rat Adjuvant Arthritis-Interstitial Lung Disease Model.

ABSTRACT

INTRODUCTION: Development of an animal model of rheumatoid arthritis-interstitial lung disease (RA-ILD) and improved knowledge of the pathogenesis of RA-ILD may facilitate earlier diagnosis and the development of more effective targeted therapies. METHODS: Adult male Wistar rats were studied in an adjuvant arthritis (AA) model induced by the injection of Freund's complete adjuvant (FCA). Rats were sacrificed on days 7, 14, 21, and 28 after FCA injection. Lung tissue was obtained for histopathological examination and evaluation of Caveolin-1 (Cav-1) and transforming growth factor-ß (TGF-ß1) protein expression levels. RESULTS: Pulmonary inflammation was evident in lung tissue from day 21 after FCA injection. Inflammation and mild fibrosis were observed in lung tissue on day 28 after FCA injection. Cav-1 protein expression was significantly decreased from day 7 through day 28 and TGF-ß1 protein expression was significantly increased on day 28 after FCA injection compared to control (P < 0.05). CONCLUSION: We established an AA rat model that exhibited the extra-articular complication of RA-ILD. We identified Cav-1 and TGF-ß1 as protein biomarkers of RA-ILD in this model and propose their signaling pathway as a possible target for therapeutic intervention.