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Daptomycin alleviates collagen-induced arthritis via suppressing inflammatory cytokines and NF-κB pathway. | LitMetric

Daptomycin alleviates collagen-induced arthritis via suppressing inflammatory cytokines and NF-κB pathway.

Int Immunopharmacol

State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, and Collaborative Innovation Center for Biotherapy, No.17, 3rd Section of People's South Road, Chengdu, 610041, PR China. Electronic address:

Published: January 2025

AI Article Synopsis

  • Rheumatoid arthritis (RA) is a chronic autoimmune disease influenced by factors like bacterial infection and immune inflammation.
  • Daptomycin (DAP), known for its antibacterial properties, is being studied for its potential anti-inflammatory effects on RA.
  • Research shows that DAP reduces inflammation in RA models by lowering key inflammatory markers and signaling pathways, suggesting its potential for broader clinical use beyond just treating infections.

Article Abstract

Rheumatoid arthritis (RA) is a chronic autoimmune disease, and its pathogenic factors include bacterial infection and immune inflammation. Daptomycin (DAP) is a cyclic lipopeptide that has been approved to treat skin infections, bacteremia and right-sided endocarditis due to its effective antibacterial effects against most Gram-positive pathogenic bacteria. Herein, we focus on whether DAP exerts anti-inflammatory activity on RA to expand DAP drug indications. Our studies are first time to evaluate anti-inflammatory effect and reveal its molecular pharmacological mechanism of DAP on lipopolysaccharide-activated macrophage and collagen-induced arthritis (CIA) mice. In vitro cytological studies show that 10 µg/mL DAP inhibits secretion of IL-1β, IL-6 and TNF-α to alleviate cell inflammation, and the phosphorylation level of p65 (p-p65) of RAW 264.7 cells is decreased under DAP exposure. Administration with 10 mg/kg/2d DAP via intravenous injection on CIA mice significantly reduces arthritis symptom by inhibiting p-p65 level and decreasing serum level of IL-6, IL-1β and TNF-α. Moreover, our study is the first time to reveal new immunomodulatory effects of DAP on RA, which provides a pharmacological basis for new clinical applications of DAP for other immune-related diseases except to bacterial infections.

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Source
http://dx.doi.org/10.1016/j.intimp.2024.113648DOI Listing

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