The role of leptin in the pathophysiology of rheumatoid arthritis

The past 20 years of research on leptin has provided important insights into its role in rheumatoid arthritis (RA). Leptin is one of the different adipokines produced by the adipose tissue that influences the endocrine system, energy homeostasis and the immune response in several ways. Leptin is known to have predominantly pro-inflammatory effects, especially in the setting of chronic inflammation. Animal models of arthritis have illustrated well the participation of leptin in the inflammatory response within the joints. In patients with RA, numerous studies have evaluated the concentrations of leptin in the bloodstream and/or the joint cavity, showing higher levels compared to control populations. Leptin has also been found to correlate with clinical or biological measurements of disease activity of RA. Conversely, the relationship between serum leptin and joint structural damage is less evident. Leptin may also promote the development of atherosclerosis in RA and may contribute to the cardiovascular consequences of the metabolic syndrome that coexists with RA. Indeed, leptin could be a link between inflammation, metabolic risk factors and cardiovascular diseases in RA. Finally, due to abnormal body composition phenotypes with an increased prevalence of obesity in RA, the therapeutic response to traditional DMARDs and/or biological agents may be attenuated. This review discusses the multiple interplays that have been described between leptin and the clinical, radiographic and therapeutic aspects of RA.