Abstract
Rheumatoid arthritis (RA) is an inflammatory joint disorder characterized by synovial proliferation and inflammation, with eventual joint destruction if inadequately treated. Modern therapies approved for RA target the proinflammatory cytokines or Janus kinases that mediate the initiation and progression of the disease. However, these agents fail to benefit all patients with RA, and many lose therapeutic responsiveness over time. More effective or adjuvant treatments are needed. Melatonin has shown beneficial activity in several animal models and clinical trials of inflammatory autoimmune diseases, but the role of melatonin is controversial in RA. Some research suggests that melatonin enhances proinflammatory activities and thus promotes disease activity in RA, while other work has documented substantial anti-inflammatory and immunoregulatory properties of melatonin in preclinical models of arthritis. In addition, disturbance of the circadian rhythm is associated with RA development and melatonin has been found to affect clock gene expression in joints of RA. This review summarizes current understanding about the immunopathogenic characteristics of melatonin in RA disease. Comprehensive consideration is required by clinical rheumatologists to balance the contradictory effects.
Highlights
Rheumatoid arthritis (RA) is an autoimmune disease that is characterized by synovial proliferation and inflammatory responses, the presence of autoantibodies including rheumatoid factor and anti-citrullinated protein antibodies (ACPA) in sera, cartilage, and bone erosion with deformity, and co-occurring health conditions such as cardiovascular disease events, pulmonary, psychological, and metabolic bone disorders [1]
Endocrine circadian rhythms are regulated by the endogenous hormone melatonin (N-acetyl5-methoxytryptamine), which activates specific high-affinity melatonin receptors expressed on several different types of cells, including immunocompetent cells [8]
The development of collagen-induced arthritis (CIA) in DBA/1 mice is exacerbated by constant darkness [39] and by daily exogenous administration of melatonin 1 mg/kg [40]
Summary
Rheumatoid arthritis (RA) is an autoimmune disease that is characterized by synovial proliferation and inflammatory responses, the presence of autoantibodies including rheumatoid factor and anti-citrullinated protein antibodies (ACPA) in sera, cartilage, and bone erosion with deformity, and co-occurring health conditions such as cardiovascular disease events, pulmonary, psychological, and metabolic bone disorders [1]. The highly efficacious biologic DMARDs targeting the proinflammatory cytokines and Janus kinase inhibitors are intended for patients with persistently active disease after initial methotrexate failure and, in some cases, another conventional DMARD [2]. These novel medications help to control RA disease activity, they are not universally effective in all RA patients [3,4] and many will lose therapeutic responsiveness after a period of time [5]. The anti-inflammatory and antioxidant effects of melatonin have proven beneficial in several inflammatory autoimmune diseases [6]. The aim of this review is to elucidate the complex reactions of melatonin in RA and determine whether melatonin could serve as a potential therapeutic agent
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