Analysis of inflammatory networks in interstitial lung disease in patients with rheumatoid arthritis

Introduction: Pulmonary involvement leading to interstitial lung disease (ILD) is the most common and potentially most devastating complication of Rheumatoid Arthritis (RA). The lifetime risk of ILD development in RA patients is approximately 10%. Still, there is very little known about the presence of pro-inflammatory and pro-fibrotic mediators and their potential involvement to disease pathophysiology. Aim: The primary objective of this study was to assess the expression of various inflammatory mediators in bronchoalveolar lavage of RA-ILD patients and compare it with that of ILD and no-ILD RA patients. The secondary objective was to assess the presence of key leads in the SKG mouse model of RA and ILD in order to study the functional relevance in disease development and progression. Methods: A total number of 15 patients were recruited to the study and divided into 3 groups 1)RA with ILD, 2)RA without ILD and 3)Idiopathic pulmonary fibrosis. Bronchoalveolar lavage fluid was obtained and analysed by Luminex and Elisa. SKG mice were also used and BAL was investigated. Results: Various inflammatory mediators including Activin A, VEGF, IL-8, MCP-1, MIP-1a and MIP-1b were found to be up-regulated in the BAL from patients with ILD-RA. Activin-A, a cytokine with both inflammatory and pro-fibrotic activity, was also abundant in BAL from SKG mice with lung fibrosis. Conclusions: Our results reveal that multiple pro-inflammatory and pro-fibrotic mediators are present in RA-ILD and raise the possibility that Activin A may also be important in the disease process.