Effect of tripterygium glycosides on pulmonary function in adjuvant arthritis rats.

ABSTRACT

BACKGROUND: Tripterygium is a Chinese herb with immunosuppressive effects and an established history of use in the treatment of rheumatoid arthritis. Previous studies demonstrated that tripterygium glycosides (TPG) alleviated Freund's complete adjuvant (FCA)-induced arthritis. Simultaneously, it has also been observed to impact the adjuvant arthritis (AA) associated with lung injury. In this study, we have investigated whether traditional Chinese medicine could attenuate lung injury induced by AA by observing the effects of TPG on the degree swelling, arthritis index (AI), lung index (LI), pulmonary function, cytokines, and the expression of regulatory T cells (Treg) and Foxp3 in AA rats. METHODS: A total of 48 rats were separated into four groups normal control (NC), model control (MC), methotrexate (MTX), and TPG groups (12 in each). Except for the rats of NC group, those in the others groups were intracutaneously injected in the right hind limb with 0.1 ml of FCA. The NC and MC groups were treated with physiological saline, and the MTX and TPG groups were treated with MTX and TPG, respectively. Thirty days after administration, the changes in swelling degree, AI, LI, pulmonary function, Treg levels, the ultrastructure of the lung tissue, and the expression of Foxp3 in the lung tissue were observed. RESULTS: Compared with NC group, the level of swelling degree, AI, LI, 1 second average expiratory flow (FEV1/FVC %), the alveolar inflammation integration, tumor necrosis factor alpha (TNF-α), and endothelium-1 (ET-1) in the MC group had significantly increased (p < 0.01). However, the level of forced vital capacity (FVC), 25% vital capacity of the peak expiratory flow (FEF25), 50% vital capacity of the peak expiratory flow (FEF50), 75% vital capacity of the peak expiratory flow (FEF75), maximum mid-expiratory flow (MMF), peak expiratory flow (PEF), interleukin-10 (IL-10), CD4(+) CD25(+) Treg, and Foxp3 had significantly decreased (p < 0.01). LI, the alveolitis score, and ET-1 were found to decrease with TPG treatment. However, the levels of FVC, FEF25, FEF50, FEF75, MMF, PEF, IL-10 in serum, and CD4(+) CD25(+) Treg in peripheral blood had increased. The expressions of Foxp3 protein and mRNA in the lung tissue had also increased in the TPG group. Compared with the MTX group, the pulmonary function had enhanced, the structure of alveolar type II cells had improved, and the expression of the IL-10, Treg, and Foxp3 had elevated. However, the TNF-α and ET-1 levels had reduced as compared to the MTX group. CONCLUSION: The level of paw swelling and AI in the AA rats can be inhibited by TPG. The inflammatory response in lung tissue had also decreased, although there was significant improvement in the pulmonary function. The mechanism that would explain this observation is probably associated with the upregulation of the expression of IL-10, Treg, and Foxp3 and downregulation of the expression of TNF-α and ET-1.