Background/Purpose:  This study aimed to determine the regulatory role of N-Acetyl-L-cysteine (NAC), an antioxidant, in T cell and osteoclast differentiation in rheumatoid arthritis (RA).

Methods:  After RA synovial fibroblasts were stimulated by LPS, the expression and production of RANKL, IL-1beta, TNF-alpha was determined by real-time PCR and ELISA. After human peripheral CD4+ T cells were cultured under Th0 condition, IL-17, IFN-g, IL-4, Foxp3, RANKL and IL-2 expression was determined by flow cytometry and ELISA. Human peripheral blood monocytes were cultured with M-CSF, RANKL, and various concentrations of NAC, followed by staining of the cells for tartrate-resistant acid phosphatase activity to determine osteoclast formation. Osteoclastogenesis was also determined after cocultures of LPS-stimulated RA synovial fibroblasts or Th0-stimulated CD4+T cells and various concentrations of NAC with human PBMC.

Results:  When RA synovial fibroblasts were stimulated by LPS, LPS stimulated their production of RANKL, IL-1beta, TNF-alpha and IL-6. NAC reduced the LPS-induced production of proinflammatory cytokines and RANKL in a dose-dependent manner. After human peripheral CD4+ T cells were cultured under Th0 polarizing condition, NAC decreased the proportion of IL-17⁺ and CD4⁺ T cells, and production of IL-17 and RANKL. When human peripheral blood CD14⁺ monocytes were cultured with M-CSF and RANKL, osteoclasts was differentiated, however, NAC significantly inhibited the osteoclastogenesis

Conclusion:  NAC inhibits the production of proinflammatory cytokines and RANKL in RA synovial fibroblasts, differentiation of osteoclasts and Th17 cells. NAC could be a new therapeutic medication for regulation of autoimmune reaction and prevention of bone destruction in RA.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/n-acetylcysteine-regulates-osteoclastogenesis-and-th17-cell-differentiation-in-rheumatoid-arthritis/