Treatment of collagen-induced arthritis by Natura-α via regulation of Th-1/Th-17 responses

Cytokines and CD4⁺ Th cells play a crucial role in the pathogenesis of rheumatoid arthritis. Among the Th populations, Th-1 and Th-17 have been described as pathogenic in collagen-induced arthritis (CIA) whereas Th-2 and Treg were found to have protective effects. The objective of this study was to examine the affect of Natura-α, a newly developed cytokine regulator, on CIA and on Th cell development. Natura-α treatment was administered before or during arthritis induction. Anti-type II collagen antibodies and cytokine expression were evaluated by ELISA. Emergence of CD4⁺CD25⁺Foxp3⁺ T cells was assessed by flow cytometry. Th-17 differentiation of naive CD4 T cells was assessed in cultures with anti-CD3 and anti-CD28. We showed that Natura-α both prevented and treated CIA. We further demonstrated that in vivo treatment with Natura-α inhibited IL-17 production and anti-type II collagen IgG development. We showed in vitro, using an APC-free system, that Natura-α acted directly on differentiating T cells and inhibiting the formation of Th-1 and Th-17 cells but did not affect Th-2 cells. Since Natura-α inhibits a large spectrum of important pathogenic factors in CIA, it may provide a new and powerful approach to the treatment of rheumatoid arthritis and other inflammatory diseases.