Immunomodulatory Activity of Resveratrol2010-02-12
Inflammation is an important pathway for human body to combat diseases; however it has its own negative side effects. Modern medical and molecular medical research has shown that chronic local inflammation is one of the triggering factors in the development of major diseases like cardiovascular diseases, tumors, arthritis, hepatocirrhosis and diabetes. Therefore, inhibiting chronic inflammation becomes a major task in controlling the development of major diseases.
Research on antiseptic effect of resveratrol has been widely reported. The earliest paper in this area was published in 1985 by the Japanese group who first isolated resveratrol from Giant Knotweed Rhizome. In this paper they described the inhibitory effect of resveratrol on inflammatory precursors of leukocytes.
★ Kimura, Y., Okuda, H., and Arichi, S. Effects of stilbenes, on arachidonate metabolism in leukocytes. Biochim. Biophys. Acta 1985; 834: 275–278.（http://www.ncbi.nlm.nih.gov/pubmed/3922423）
Shortly after 10 years, wider and comprehensive research works followed in the wake of this century. It was found that resveratrol has pleiotropic effects on immunity: inhibitory effect on the proliferation of lymphocytes, enhancing the activity of cytotoxic T lymphocytes and the secretions of multiple cytokines, and especially its effect of NF-kB transcriptional regulation which is closely associated to tumorigenesis and this further strengthens our notion that resveratrol helps suppress tumors by regulating the immune system.
★ Gao X, et al. Immunomodulatory activity of resveratrol: suppression of lymphocyte proliferation, development of cell-mediated cytotoxicity, and cytokine production. Biochem Pharmacol 2001; 62: 1299–1308
★ Tsai SH, et al. Suppression of nitric oxide synthase and the down-regulation of the activation of NF-kB in macrophages by resveratrol. Br. J. Pharmacol 1999; 126: 673–680. (http://www3.interscience.wiley.com/cgi-bin/fulltext/121664749/PDFSTART )
★ Falchetti R, et al. Effects of resveratrol on human immune cell function. Life Sci 2001; 70: 81–96. (http://www.ncbi.nlm.nih.gov/pubmed/11764009)
★ Pellegatta F, et al. Different short- and long-term effects of resveratrol on nuclear factor-kB phosphorylation and nuclear appearance in human endothelial cells. Am J Clin Nutr 2003; 77: 1220–1228. (http://www.ajcn.org/cgi/reprint/77/5/1220)
★ Csiszar A, et al. Resveratrol attenuates TNF-a-induced activation of coronary arterial endothelial cells: role of NF-kB inhibition. Am J Physiol Heart Circ Physiol 2006; 291: H1694–H1699. (http://ajpheart.physiology.org/cgi/reprint/291/4/H1694.pdf)
★ Heynekamp JJ, et al. Substituted trans-stilbenes, including analogues of the natural product resveratrol, inhibit the human tumor necrosis factor alpha-induced activation of transcription factor nuclear factor KappaB. J Med Chem. 2006; 49: 7182-7189. （http://pubs.acs.org/doi/abs/10.1021/jm060630x）
Many incurable diseases are autoimmune diseases related. Autoimmunity means the T cells in the human immune system attack the cells in the own body. Tumor will not occur and develop if T lymphocytes attack the tumor cells. However, they often attack other important cells in the human body, for example, the insulin-secreting β-cells, and this will lead to Type I diabetes.
Autoimmunity disease is due to the overactivation of some subsets of T cells which are not controlled at proper level. Modern immunology research has clearly shown that CD28/CTLA-4 on the T cells is the only pathway to inhibit the self-destructing T cells. Resveratrol, together with curcumin, has been proven to inhibit overactivated T cell immunity, which means resveratrol can be used to treat autoimmune diseases, such as systemic lupus erythematosus (SLE), aplastic anemia, Type I diabetes and rheumatoid arthritis.
★ Sharma S, et al. Resveratrol and curcumin suppress immune response through CD28/ CTLA-4 and CD80 co-stimulatory pathway. Clin Exp Immunol 2006; 147: 155–163. (http://www.pubmedcentral.nih.gov/picrender.fcgi?artid=1810449&blobtype=pdf)