Adipocytokines in Rheumatoid Arthritis: The Hidden Link between Inflammation and Cardiometabolic Comorbidities

Abstract

Rheumatoid arthritis is a chronic autoimmune disease affecting typically synovial joints and leading to progressive articular damage, disability, and reduced quality of life. Despite better recent therapeutic strategies improving long-term outcomes, RA is associated with a high rate of comorbidities, infections, malignancies, and cardiovascular disease (CVD). Remarkably, some well-known pathogenic proinflammatory mediators in RA, such as interleukin-1β (IL-1β) and tumor necrosis factor (TNF), may play a pivotal role in the development of CVD. Interestingly, different preclinical and clinical studies have suggested that biologic agents commonly used to treat RA patients may be effective in improving CVD. In this context, the contribution of adipocytokines has been suggested. Adipocytokines are pleiotropic molecules, mainly released by white adipose tissue and immune cells. Adipocytokines modulate the function of different tissues and cells, and in addition to energy homeostasis and metabolism, amplify inflammation, immune response, and tissue damage. Adipocytokines may contribute to the proinflammatory state in RA patients and development of bone damage. Furthermore, they could be associated with the occurrence of CVD. In this study, we reviewed available evidence about adipocytokines in RA, because of their involvement in disease activity, associated CVD, and possible biomarkers of prognosis and treatment outcome and because of their potential as a possible new therapeutic target.

Figure 1

Schematic role of adipocytokines on the relationship among adipose tissue, rheumatoid arthritis, and atherosclerotic process.

Figure 2

Pathogenic mechanisms of adipocytokines in rheumatoid arthritis and cardiometabolic diseases. Abbreviations: T Reg cells—T regulatory cells; TCR—T-cell receptor; NK cells—natural killer cells; TNF—tumor necrosis factor; IL—interleukin; MMP—metalloproteinase.