Zhiping Yu,1,2,* Ji Liu,1,* Letian Chen,2,* Junping Xie1 

1Department of Respiratory and Critical Care Medicine, Second Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, People’s Republic of China; 2Department of Respiratory and Critical Care Medicine, Yingtan People’s Hospital, Yingtan, Jiangxi, People’s Republic of China

*These authors contributed equally to this work

Correspondence: Junping Xie, Department of Respiratory and Critical Care Medicine, Second Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, People’s Republic of China, Email junpingxie@sina.com

Abstract: Rheumatoid arthritis (RA) is a systemic autoimmune disorder characterized by chronic synovitis and extra-articular manifestations (EAMs), with interstitial lung disease (ILD) being a leading cause of mortality. Interleukin-6 (IL-6), a pivotal cytokine in RA pathogenesis, drives both articular and pulmonary inflammation through its involvement in immune dysregulation and fibrotic processes. This review elucidates the molecular mechanisms by which IL-6 contributes to rheumatoid arthritis-associated interstitial lung disease (RA-ILD) progression, particularly via the Janus kinases (JAK)/signal transducers and activators of transcription (STAT) signaling pathway and macrophage polarization. Additionally, we objectively evaluate current and emerging therapeutic strategies targeting IL-6 and downstream pathways.

Keywords: IL-6, RA-ILD, JAK/STAT signaling, macrophage polarization, targeted therapy