A novel artemisinin derivative, 3-(12-β-artemisininoxy) phenoxyl succinic acid (SM735), mediates immunosuppressive effects in vitro and in vivo

• 来源期刊: 中国药理学报（英文版）
• 关键词: artemisinin non-steroidal anti-inflammatory agents SM735 immuno-suppressive activity
• 年，卷（期）: 2005,（11）
• 页码范围: 1352-1358
• 页数: 7页
• 语种: 英文

摘要

Aim: To study the immunosuppressive activity of SM735 { [3-(12-β-artemisininoxy)]phenoxyl succinic acid }, a synthetic artemisinin derivative with nonsteroidal anti-inflammatory drug structure, with the aim of finding potential immunosuppressiveagents. Methods: Concanavalin A (ConA), lipopolysaccharide (LPS), and mixedlymphocyte reaction (MLR), were used to induce the proliferation of splenocytes,and [3H]-thymidine incorporation was used to evaluate the proliferation ofsplenocytes. Cytokine production was promoted with ConA, LPS, or PMA plusionomycin, and was detected with the enzyme-linked immunosorbent assay.Dinitrofluorobenzene (DNFB) and sheep red blood cells (SRBC) were used toinduce delayed-type hypersensitivity and quantitative hemolysis of SRBC (QHS)mouse models, as criteria for the evaluation of in vivo immune activity. Results:SM735 strongly inhibited the proliferation of splenocytes induced by ConA, LPS,or MLR, with IC50 values of 0.33 μmol/L, 0.27 μmol/L, and 0.51 μmol/L, respectively.When compared with a CC50 value of 53.1 μmol/L, SM735 had a favorable safetyrange. SM735 dose-dependently inhibited proinflammatory cytokine production[including interleukins (IL)-12, interferon (IFN)-γ and IL-6] induced by LPS orPMA plus ionomycin. Upon ConA stimulation, SM735 suppressed IFN-γ in adose-dependent manner, but did not affect IL-2 secretion. SM735 also stronglysuppressed both T-cell-mediated delayed-type hypersensitivity (DTH) and B-cell-mediated QHS reactions. Conclusion: SM735 had strong immunosuppres-sive activity in vitro and in vivo, suggesting a potential role for SM735 as animmunosuppressive agent, and established the groundwork for further researchon SM735.