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Rheumatoid arthritis is a chronic inflammatory disease associated with joint inflammation and destruction driven by T helper 17 (Th17) cells. Interleukin‐6 (IL‐6) is secreted by many cell types, including macrophages and synovial fibroblasts. It induces the differentiation and function of Th17 cells that can increase lymphocytic infiltration in the joint. LMT‐28 can suppress IL‐6 signalling through direct binding to glycoprotein‐130 and alleviate inflammatory diseases such as rheumatoid arthritis and inflammatory bowel disease. The purpose of this study was to assess whether LMT‐28 could potently inhibit Th17 differentiation and to determine the mechanism involved in the attenuating effect of LMT‐28 on rheumatoid arthritis through the IL‐6 signalling pathway. LMT‐28 reduced the arthritis score and showed protective effects against bone and cartilage destruction in collagen‐induced arthritis (CIA) mice. In mice with CIA, LMT‐28 markedly decreased serum levels of IL‐6, TNF and IL‐1β compared to vehicle control. Moreover, LMT‐28 attenuated Th17 cell activation in lymph nodes of CIA mice. We demonstrated that LMT‐28 suppressed differentiation of Th17 in mouse splenocytes and human peripheral blood mononuclear cells (PBMCs). Additionally, LMT‐28 inhibited phosphorylation of GP130, STAT3 and ERK induced by Hyper‐IL‐6 in human fibroblast‐like synoviocytes (FLS). Collectively, these results suggest that LMT‐28 can inhibit differentiated/activated‐Th17 cells in rheumatoid arthritis by blocking activation of the STAT3 pathway. LMT‐28 can attenuate rheumatoid arthritis by inhibiting differentiation/activation of Th17 cells and suppressing the proliferation and signalling activation of the IL‐6/solubleIL‐6 receptor complex stimulated FLS. [ABSTRACT FROM AUTHOR]

Antiplatelet drugs are conventionally used as treatments because of their anti‐coagulation functions. However, their pleiotropic effects are of great significance to the treatment of ischaemic cardiovascular diseases. Many studies have reported that an excessive amount of inflammation driven by tumour necrosis factor (TNF) is closely related to the prevalence of atherosclerosis. As the drug selection criteria and evaluation methods related to the anti‐TNF activity of antiplatelet drugs remain limited, our investigation of these drugs should prove beneficial. In this study, we compared the anti‐TNF activity of three antiplatelet agents, namely clopidogrel, sarpogrelate, and cilostazol, using the TNF‐induced inflammatory mouse model. After the oral administration of these drugs, acute inflammation was induced via injection of lipopolysaccharide (LPS) or D‐galactosamine (D‐gal) and TNF. Serum TNF levels, and the mRNA and protein expression levels of TNF in mouse heart tissue, macrophage accumulation in aortic lesions, and mouse survival were analysed to compare the anti‐TNF effects of the three antiplatelet agents. Of the three antiplatelet agents, cilostazol significantly reduced the different levels under the most effective observation. In addition, cilostazol was found to attenuate the TNF‐stimulated phosphorylation of mitogen‐activated protein kinase (MAPK) and nuclear factor kappa‐light‐chain‐enhancer of activated B cell (NF‐κB) p65 in the aortic vascular smooth muscle cell line, MOVAS‐1 and the D‐gal plus TNF‐challenged heart tissue of mouse. Therefore, cilostazol is the most ideal of the three antiplatelet drugs for the treatment of TNF‐mediated inflammatory disorders. [ABSTRACT FROM AUTHOR]