Cytokine Pathways Driving Diverse Tissue Pathologies in Rheumatoid Arthritis

Rheumatoid arthritis (RA) is a complex systemic disorder characterized primarily by articular inflammation and destruction with associated functional loss and reduced quality of life. RA is also associated with extra-articular disease, such as that of the lung, with potentially devastating clinical consequences. The critical importance of comorbidities, and consequent multimorbidity, in determining outcomes in RA has now been recognized, not least as novel therapeutics have emerged with attendant increased life expectancy. The primary role of cytokine networks in mediating RA pathogenesis was established in extensive preclinical and clinical trials and in the adoption of cytokine-targeted therapeutics in clinical care over three decades. Herein, we briefly review those pivotal cytokine pathways that are associated with RA articular disease and extend these insights to include extra-articular RA and its common comorbidities.