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

Abstract

AIM:

To study the immunosuppressive activity of SM735 {[3-(12-beta-artemisininoxy)] phenoxyl succinic acid}, a synthetic artemisinin derivative with nonsteroidal anti-inflammatory drug structure, with the aim of finding potential immunosuppressive agents.

METHODS:

Concanavalin A (ConA), lipopolysaccharide (LPS), and mixed lymphocyte reaction (MLR), were used to induce the proliferation of splenocytes, and [3H]-thymidine incorporation was used to evaluate the proliferation of splenocytes. Cytokine production was promoted with ConA, LPS, or PMA plus ionomycin, and was detected with the enzyme-linked immunosorbent assay. Dinitrofluorobenzene (DNFB) and sheep red blood cells (SRBC) were used to induce 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 IC(50) values of 0.33 micromol/L, 0.27 micromol/L, and 0.51 micromol/L, respectively. When compared with a CC(50) value of 53.1 micromol/L, SM735 had a favorable safety range. SM735 dose-dependently inhibited proinflammatory cytokine production [including interleukins (IL)-12, interferon (IFN)-gamma and IL-6] induced by LPS or PMA plus ionomycin. Upon ConA stimulation, SM735 suppressed IFN-gamma in a dose-dependent manner, but did not affect IL-2 secretion. SM735 also strongly suppressed both T-cell-mediated delayed-type hypersensitivity (DTH) and B-cell-mediated QHS reactions.

CONCLUSION:

SM735 had strong immunosuppressive activity in vitro and in vivo, suggesting a potential role for SM735 as an immunosuppressive agent, and established the groundwork for further research on SM735.

• Authors: Wen-liang Zhou, Jin-ming Wu, Qing-li Wu, Jun-xia Wang, Yu Zhou, Ru Zhou, Pei-lan He, Xiao-yu Li, Yi-fu Yang, Yu Zhang, Ying Li, Jian-ping Zuo
• Journal: Acta pharmacologica Sinica (Acta Pharmacol Sin) Vol. 26 Issue 11 Pg. 1352-8 (Nov 2005) ISSN: 1671-4083 [Print] United States
• PMID: 16225758 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• 3-(12-beta-artemisininoxy) phenoxyl succinic acid
• Anti-Inflammatory Agents, Non-Steroidal
• Artemisinins
• Cytokines
• Immunosuppressive Agents
• Succinates
• Interleukin-12
• Interferon-gamma

Topics

• Animals
• Anti-Inflammatory Agents, Non-Steroidal (chemistry)
• Artemisinins (administration & dosage, pharmacology)
• Cell Proliferation (drug effects)
• Cells, Cultured
• Cytokines (metabolism)
• Dose-Response Relationship, Drug
• Hemolysis (drug effects)
• Hypersensitivity, Delayed (chemically induced, prevention & control)
• Immunosuppressive Agents (administration & dosage, pharmacology)
• Inhibitory Concentration 50
• Interferon-gamma (metabolism)
• Interleukin-12 (metabolism)
• Lymphocyte Culture Test, Mixed
• Male
• Mice
• Mice, Inbred BALB C
• Mice, Inbred C57BL
• Succinates (administration & dosage, pharmacology)