Introduction Aberrant T-cell responses are crucially involved in the pathogenesis of systemic autoimmune diseases such as rheumatoid arthritis (RA) leading to chronic inflammation and organ damage. Resveratrol is a natural occuring polyphenol mainly produced in plants. The beneficial effects of resveratrol are due to its anti-inflammatory, anti-carcinogenic and anti-oxidant activities. The aim of this study was to investigate the effects of resveratrol and a novel resveratrol-salicylate hybrid molecule (C10) on human CD4+ T-cells.
Methods CD4+ T-cells from healthy donors were pre-incubated with different concentrations of resveratrol or C-10 before being stimulated with anti-CD3/anti-CD28 antibodies. After 24 h and 72 h, respectively, cell culture supernatants were harvested and IL-2, IFN-γ and TNF-α release were quantified by ELISA. Proliferation rate was measured by thymidine incorporation. In addition, the up-regulation of the early activation markers CD25, CD69, CD71 and CD98 was analysed and phosphorylation of the MAP-kinase ERK as well as AKT and SRP6 was determined by westernblot or flow cytometry.
Results Inhibition of IL-2, IFN-γ and TNF-α release was significantly more effective when the cells were treated with C-10 (p < 0.05). In comparison to the untreated control, C-10 inhibited cytokine production by 35% (6.25 µM), by 55% (12.5 µM) or by 80% (25 µM) whereas resveratrol inhibited cytokine production only at 25 µM or 50 µM significantly. Moreover, proliferation rate in CD4+ T-cells was significantly more decreased in the presence of C-10 at concentrations of 25 µM or 50 µM (p < 0.0001). The expression of the early activation markers CD25, CD69, CD71 and CD98 was reduced in a dose dependent manner when the cells were exposed to resveratrol or C-10. Furthermore, the phosphorylation of ERK, Akt and S6RP was attenuated by resveratrol or C-10 to a similar degree.
Conclusion Resveratrol and C-10 both suppressed cytokine secretion and proliferation of CD4+ T-cells. The suppressive effects appear to be based on partial suppression of phosphorylation of several important signalling molecules involved in cytokine expression and cell growth. Since C-10 significantly amplified the effects of resveratrol these data suggest C-10 as an interesting candidate drug for treatment of RA and other T cell driven autoimmune diseases.