CD4+ regulatory T (Treg) cells and T-helper 17 (Th17) cells have been shown to have important roles in rheumatoid arthritis (RA). In our previous study, it was demonstrated that artesunate was able to alter the Treg/Th17 ratio in patients with RA; however, the underlying mechanisms remain unclear. The present study established a male Sprague Dawley (SD) rat model of type II collagen-induced arthritis (CIA). SD rats were divided into normal control, CIA model and artesunate-treated (5, 10 or 20 mg/kg/day) groups. Treg and Th17 cells were detected in the synovium by immunohistochemical analysis of forkhead/winged helix transcription factor (Foxp3) and interleukin (IL)-17 expression. Subsequently, lymphocytes were extracted from the rat spleens, and the proportions of Treg/Th17 cells were detected by flow cytometry. The results demonstrated that the expression levels of Foxp3 were significantly decreased, and those of IL-17 were significantly increased, in the CIA model group, as compared with the normal control group. The results demonstrated that artesunate decreased the frequency of Th17 cells and increased the frequency of Treg cells in CIA rats in a dose-dependent manner. In conclusion, the present study suggested that artesunate may regulate the Th17/Treg balance by inducing Th17-mediated apoptosis. Therefore, artesunate may be considered a novel therapeutic agent for the treatment of patients with RA.

The objective of the study was to investigate whether the immunological factors in patients with Systemic Lupus Erythematosus (SLE) and a high incidence of atherosclerosis correlate with a Th17/Treg imbalance. All cases were recruited from the Affiliated Hospital of Guilin Medical University: a random sample of 42 cases with SLE and atherosclerosis, 39 positive control cases with SLE alone with no anomalies detected via coronary artery angiography or carotid color Doppler ultrasound examination, as well as 45 normal controls based on physical examination were included. The serum expression levels of IL-10, IL-17, IL-6, TNF-α, Th17, Th17 cell transcription factor RORγt, and Treg cell transcription factor Foxp3 were measured in each group of patients. Correlations among Th17/Treg, their secreted cell factors, transcription factors, SLE, and SLE with concurrent atherosclerosis (SLE + AS) were analyzed. The results are as follows: (1) total cholesterol and triacylglycerol levels in the SLE and SLE + AS groups were higher than those in the control group (P < 0.05 and P < 0.01); (2) serum IL-10 in the SLE + AS group was lower than the SLE and control groups; however, serum IL-17 and IL-6 levels in the SLE + AS group were elevated compared to the SLE and control groups (average P < 0.01); (3) the percentage of Treg cells in the SLE + AS patients was lower than those found in the SLE and control groups; in contrast, percentages of serum Th17 cells in SLE + AS patients were higher than the SLE and control groups (average P < 0.01); (4) FoxP3 expression in the SLE + AS group was lower than levels observed in the SLE and control groups (average P < 0.05); in contrast, RORγt expression in the SLE + AS group was higher than levels found in the SLE and control groups (average P < 0.05). The abnormal balance between Th17 cells and Treg cells in SLE + AS patients has obvious implications for Th17 migration. The results suggest that Th17 cell proportion and function can be enhanced, relatively or absolutely, whereas the proportion and function of Treg cells can abate, relatively or absolutely. This imbalance may be an important reason for the high incidence of SLE with atherosclerosis.

Artesunate could increase the expression of Foxp3 in a dose-dependent manner, and thus reduce pannus formation and erosion of cartilage and bone to prevent lesions from rheumatoid arthritis.

The objective of the study is to investigate the mechanisms of cyclophosphamide sequential therapy for patient with primary Sjögren's syndrome-associated interstitial lung disease (PSS-ILD). This was a retrospective review of 15 patients (2005-2008) with PSS-ILD who underwent cyclophosphamide sequential therapy. Peripheral blood and bronchoalveolar lavage (BALF) were obtained before and 3, 6, 12 and 24 months after the treatment. The TNF-α and TGF-β1 mRNA levels in peripheral blood were measured using reverse transcription polymerase chain reaction. Serum and BALF TNF-α, TGF-β1 and MMP-9 levels were measured using sandwich enzyme-linked immunosorbent assay. The average levels of serum TNF-α (0.39 ± 0.22) and TGF-β1 (0.31 ± 0.18) mRNA in patients with PSS-ILD were higher compared with that in patients with PSS without ILD. TNF-α level (0.23 ± 0.19) was significantly decreased 3 months after cyclophosphamide treatment (t = 2.533, p < 0.05), and TGF-β1 (0.31 ± 0.18) level markedly decreased after 6 months of treatment (t = 2.617, p < 0.05). The levels of serum TNF-α (11.2 ± 2.6) μg/L, TGF-β1 (72 ± 19) μg/L and MMP-9 (38 ± 9) μg/L in patients with PSS-ILD were higher than that in patients with PSS without ILD. TGF-β1 (36 ± 12) μg/L level decreased significantly after 3 months of treatment (t = 2.526, p < 0.05), and TNF-α level (7.1 ± 1.3) μg/L markedly decreased after 6 months of therapy (t = 2.578, p < 0.05). MMP-9 level (18 ± 4) μg/L decreased significantly after 12-month treatment (t = 2.329, p < 0.05). The levels of BALF TNF-α (17.1 ± 3.5) μg/L, TGF-β1 (36 ± 17) μg/L and MMP-9 (27 ± 10) μg/L in patients with PSS-ILD were higher than that in patients with PSS without ILD. TGF-β1 (21 ± 14) μg/L level decreased significantly after 3-month treatment, and TNF-α level (9.4 ± 1.7) μg/L was decreased after 6 months of cyclophosphamide treatment that may be associated with its inhabitation on production of TNF-α, TGF-β1 and MMP-9.