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J Pineal Res. 2019 Apr;66(3):e12560. doi: 10.1111/jpi.12560. Epub 2019 Feb 14.

Melatonin attenuates TNF-α and IL-1β expression in synovial fibroblasts and diminishes cartilage degradation: Implications for the treatment of rheumatoid arthritis.

Huang CC1,2, Chiou CH3, Liu SC4, Hu SL4,5, Su CM6, Tsai CH4,7, Tang CH1,3,4,8,9.

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Graduate Institute of Clinical Medical Science, China Medical University, Taichung, Taiwan.
Division of Immunology and Rheumatology, Department of Internal Medicine, China Medical University Hospital, Taichung, Taiwan.
Graduate Institute of Biomedical Sciences, China Medical University, Taichung, Taiwan.
School of Medicine, China Medical University, Taichung, Taiwan.
Department of Family Medicine, China Medical University Hospital, Taichung, Taiwan.
Department of Biomedical Sciences Laboratory, Affiliated Dongyang Hospital of Wenzhou Medical University, Dongyang, China.
Department of Orthopedic Surgery, China Medical University Hospital, Taichung, Taiwan.
Chinese Medicine Research Center, China Medical University, Taichung, Taiwan.
Department of Biotechnology, College of Health Science, Asia University, Taichung, Taiwan.


The hormone melatonin has many properties, including antioxidant, anti-inflammatory, and immunomodulatory effects. Melatonin has been demonstrated to be beneficial in several inflammatory autoimmune diseases, but its effects in rheumatoid arthritis (RA) remain controversial. We sought to determine how melatonin regulates inflammation in RA. We found that melatonin dose-dependently inhibits tumor necrosis factor-α (TNF-α) and interleukin (IL)-1β expression through the PI3K/AKT, ERK, and NF-κB signaling pathways. We also identified that melatonin inhibits TNF-α and IL-1β production by upregulating miR-3150a-3p expression. Synovial tissue specimens from RA patients and culture of human rheumatoid fibroblast-like synoviocytes confirmed that the MT1 receptor is needed for the anti-inflammatory activities of melatonin. Importantly, melatonin also significantly reduced paw swelling, cartilage degradation, and bone erosion in the collagen-induced arthritis mouse model. Our results indicate that melatonin ameliorates RA by inhibiting TNF-α and IL-1β production through downregulation of the PI3K/AKT, ERK, NF-κB signaling pathways, as well as miR-3150a-3p overexpression. The role of melatonin as an adjuvant treatment in patients with RA deserves further clinical studies.


IL-1β; TNF-α; melatonin; miR-3150a-3p; rheumatoid arthritis

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