Background/aims: Rheumatoid arthritis is a chronic autoimmune disease hallmarked by inflammation in synovial joints. Treatment is hampered by the lack of a cure and current disease-modifying drugs are associated with potentially severe toxicities.
Methods: We investigated arthritis severity by measuring joint swelling and pro-inflammatory cytokine production in a murine experimental model of inflammatory arthritis (antigen-induced arthritis). We analyzed acid sphingomyelinase knock-out mice and wild-type littermates, as well as mice treated with the pharmacological acid sphingomyelinase inhibitor amitriptyline.
Results: Genetic ablation or pharmacological inhibition of acid sphingomyelinase reduced joint swelling and levels of pro-inflammatory cytokines in the arthritic joint.
Conclusion: We identified acid sphingomyelinase as a novel druggable target in rheumatoid arthritis. Functional inhibitors of acid sphingomyelinase have been clinically used for decades, are well tolerated and suitable for long-term treatment. They would be immediately available for clinical development as a novel rheumatoid arthritis therapy.
Keywords: Acid sphingomyelinase; Ceramide; Inflammation; Rheumatoid arthritis.
© 2017 The Author(s). Published by S. Karger AG, Basel.