Immunomodulatory activity of resveratrol: discrepant in vitro and in vivo immunological effects.
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 microM. 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.
Gao
Xiaohua
X
Division of Hematology/Oncology, Department of Medicine, K-13, Henry Ford Health System, 2799 West Grand Boulevard, Detroit, MI 48202, USA.
Deeb
Dorrah
D
Media
Joseph
J
Divine
George
G
Jiang
Hao
H
Chapman
Robert A
RA
Gautam
Subhash C
SC
D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D002455:Cell Division / Q000187:drug effects; D016207:Cytokines / Q000187:drug effects / Q000378:metabolism*; D006412:Hematopoietic Stem Cells / Q000187:drug effects*; D007109:Immunity / Q000187:drug effects*; D007371:Interferon-gamma / Q000378:metabolism; D018664:Interleukin-12 / Q000378:metabolism; D007376:Interleukin-2 / Q000378:metabolism; D008213:Lymphocyte Activation / Q000187:drug effects; D008214:Lymphocytes / Q000187:drug effects*; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D000077185:Resveratrol; D013267:Stilbenes / Q000494:pharmacology*
D000975:Antioxidants; D016207:Cytokines; D007376:Interleukin-2; D013267:Stilbenes; D018664:Interleukin-12; D007371:Interferon-gamma; D000077185:Resveratrol