期刊
AMERICAN JOURNAL OF PHYSIOLOGY-LUNG CELLULAR AND MOLECULAR PHYSIOLOGY
卷 314, 期 6, 页码 L998-L1009出版社
AMER PHYSIOLOGICAL SOC
DOI: 10.1152/ajplung.00304.2017
关键词
inflammation; interstitial lung disease; rheumatoid arthritis; SKG mice
资金
- Boehringer Ingelheim Pharma [DE811138149]
- National Heart, Lung, and Blood Institute [HL-114754]
- Department of Veterans Affairs Career Development Award [2 1IK2BX002401-01A2]
Rheumatoid arthritis (RA)-associated interstitial lung disease (RA-ILD) develops in similar to 20% of patients with RA. SKG mice, which are genetically prone to development of autoimmune arthritis, develop a pulmonary interstitial pneumonia that resembles human cellular and fibrotic nonspecific interstitial pneumonia. Nintedanib, a tyrosine kinase inhibitor approved for treatment of idiopathic pulmonary fibrosis, has been shown to reduce the decline in lung function. Therefore, we investigated the effect of nintedanib on development of pulmonary fibrosis and joint disease in female SKG mice with arthritis induced by intraperitoneal injection of zymosan (5 mg). Nintedanib (60 mg.kg(-1).day(-1) via oral gavage) was started 5 or 10 wk after injection of zymosan. Arthritis and lung fibrosis outcome measures were assessed after 6 wk of treatment with nintedanib. A significant reduction in lung collagen levels, determined by measuring hydroxyproline levels and staining for collagen, was observed after 6 wk in nintedanib-treated mice with established arthritis and lung disease. Early intervention with nintedanib significantly reduced development of arthritis based on joint assessment and high-resolution mu-CT. This study impacts the RA and ILD fields by facilitating identification of a therapeutic treatment that may improve both diseases. As this model replicates the characteristics of RA-ILD, the results may he translatable to the human disease.
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