Role of Interleukin-6 in Rheumatoid Arthritis-Associated Interstitial Lung Disease: Focus on the JAK/STAT Pathway and Macrophage Polarization

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.