Immunomodulatory activity of resveratrol:: discrepant in vitro and in vivo immunological effects

被引:56
作者
Gao, XH
Deeb, D
Media, J
Divine, G
Jiang, H
Chapman, RA
Gautam, SC
机构
[1] Henry Ford Hlth Syst, Dept Med, Div Hematol Oncol, Detroit, MI 48202 USA
[2] Dept Biostat & Res Epidemiol, Detroit, MI USA
[3] Henry Ford Hlth Syst, Dept Neurol, Detroit, MI USA
关键词
resveratrol; immunomodulation; cell-mediated cytotoxicity; lymphocyte proliferation; colony-forming units; cytokines;
D O I
10.1016/j.bcp.2003.08.008
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
trans-Resveratrol is a dietary polyphenolic compound present in grapes, which has been shown to exhibit strong anti-inflammatory, antioxidant, and chemopreventive activities. In this study we have compared the in vitro and in vivo effects of resveratrol on the development of various cell-mediated immune responses, including mitogen/antigen-induced T cell proliferation, induction of cytotoxic T lymphocytes (CTLs), interleukin-2 (IL-2) induced lymphokine activated killer cells, and cytokine production. We found significant suppression (>90%) of the mitogen/antigen-induced T cell proliferation and development of allo-antigen specific CTLs in vitro with resveratrol at a concentration of 25 muM. Intragastric administration of resveratrol (2 mg daily) to mice for 4 weeks showed no effect on age-related gain in body weight, peripheral blood cell counts (WBC, RBC, or platelets), or the cellularity of bone marrow or spleen. The CD4(+) and CD8(+) T cells in spleen or colony-forming units-total in the marrow also remained unaffected by treatment with resveratrol. Spleen cells, which were stimulated in vitro after being removed from mice which had been administered resveratrol for 2 or 4 weeks, showed no significant change in IL-2 or concanavalin A induced proliferation of T cells or production of IL-2 induced lymphokine activated killer cells. Further, the production of in interferon-gamma and IL-12 was not affected by administration of resveratrol, but production of tumor necrosis factor-alpha was reduced. Even when conducted entirely in vivo, treatment with resveratrol was found to only marginally reduce allo-antigen induced T cell proliferation and the generation of CTLs in the draining lymph nodes. Thus, even though resveratrol strongly inhibits T cell proliferation and production of cytolytic cells in vitro, oral administration of resveratrol for 4 weeks does not induce hematologic or hematopoietic toxicity, and only marginally reduces the T cell-mediated immune responses. (C) 2003 Elsevier Inc. All rights reserved.
引用
收藏
页码:2427 / 2435
页数:9
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