T-614 inhibits human aortic adventitial fibroblast proliferation and promotes interleukin-8 production in vitro:

Objectives The effect and underlying mechanism of T-614 (iguratimod) on Takayasu's arteritis (TA) are unknown. Here, we report the effects of T-614 on cell proliferation and interleukin-8 (IL-8) production in human aortic adventitial fibroblasts (HAAFs) in vitro and explore its initial benefit in terms of vascular wall inflammation and remodeling for patients with TA. Methods HAAFs were cultured with 0, 5, 50, 100, or 250 mu g/ml T-614 in the absence or presence of tumor necrosis factor-alpha (TNF-alpha) in vitro. Cell viability was determined by a modified MTT assay. Supernatant IL-8 levels were measured by enzyme-linked immunosorbent assays. Results In the presence of TNF-alpha, compared to that in the control group, cell viability of HAAFs significantly decreased in the 50, 100, and 250 mu g/ml T-614 treatment groups (OD value: P < 0.01, P < 0.001, P < 0.001, respectively; survival fraction (SF): P < 0.05, P < 0.001, P < 0.001, respectively). However, there was no significant difference in cell viability between TNF-alpha-stimulated and unstimulated groups at the same concentration of T-614. In the absence or presence of TNF-alpha, T-614 suppressed HAAF cell viability dose-dependently (OD value: r = -0.915, P = 0.000; r = -0.926, P = 0.000, respectively; SF: r = -0.897, P = 0.000; r = -0.885, P = 0.000, respectively). Compared to that in the control group, in the absence of TNF-alpha, IL-8 levels in the 5 and 100 mu g/ml T-614-treated groups were significantly higher (P < 0.05); in the presence of TNF-alpha, IL-8 levels in the 5, 50, and 100 mu g/ml T-614-treated groups were significantly higher (P < 0.001, P < 0.001, P < 0.01, respectively). Further, there was a negative correlation between supernatant IL-8 levels and T-614 concentration in groups stimulated with TNF-alpha (r = -0.670, P = 0.000), but there was no significant correlation between these parameters in groups that were not stimulated with TNF-alpha. Conclusions In the absence or presence of TNF-alpha, T-614 can inhibit HAAF proliferation and promote IL-8 production in vitro; therefore, it could be used to prevent adventitial thickening of the aorta and improve vascular remodeling in inflammatory environments in vitro and might provide a new immunotherapeutic intervention for TA.