L Gloyer1, V Golumba-Nagy1, A Meyer1, S Yan1, J Schiller2, M Breuninger2, D Jochimsen2, D M Kofler1,2. 1. Laboratory of Molecular Immunology, Department I of Internal Medicine, University of Cologne, Cologne, Germany. 2. Division of Clinical Immunology and Rheumatology, Department I of Internal Medicine, University of Cologne, and Center for Integrated Oncology Aachen Bonn Cologne Duesseldorf, Cologne, Germany.
Abstract
OBJECTIVE: Studies indicate that caffeine uptake may be a risk factor for rheumatoid arthritis (RA), but a definitive link between caffeine consumption and RA has not been established. This study aimed to investigate the interplay between caffeine, adenosine receptor A2a, and interferon-γ (IFN-γ) production in CD4+ T cells from RA patients. METHOD: Peripheral blood mononuclear cells were obtained from the peripheral blood of healthy individuals and patients with RA. CD4+ T cells were isolated using the magnetic activated cell sorting technique and cultured in vitro with caffeine or mock control. In addition, adenosine was used as a competitive inhibitor of caffeine. After 48 h, expression of IFN-γ and interleukin-17 (IL-17) was analysed by flow cytometry. Ex vivo expression levels of adenosine receptor A2a were also assessed. RESULTS: Caffeine promoted IFN-γ production in Th1 cells in vitro. Significantly higher concentrations of caffeine were required to increase IFN-γ levels in Th1 cells from healthy individuals compared to Th1 cells from patients with RA. Moreover, ex vivo levels of adenosine receptor A2a expression on CD4+ T cells were significantly higher in RA than in healthy individuals. Caffeine-driven IFN-γ production was completely reversed by adenosine, a competitive agonist of adenosine receptor A2a. In contrast to IFN-γ, production of IL-17 was not affected by caffeine. CONCLUSION: Caffeine promotes IFN-γ production in Th1 cells from RA patients in vitro by competitive inhibition of adenosine receptor A2a. Excessive coffee consumption could contribute to T-cell activation and inflammation in RA.
OBJECTIVE: Studies indicate that caffeine uptake may be a risk factor for rheumatoid arthritis (RA), but a definitive link between caffeine consumption and RA has not been established. This study aimed to investigate the interplay between caffeine, adenosine receptor A2a, and interferon-γ (IFN-γ) production in CD4+ T cells from RA patients. METHOD: Peripheral blood mononuclear cells were obtained from the peripheral blood of healthy individuals and patients with RA. CD4+ T cells were isolated using the magnetic activated cell sorting technique and cultured in vitro with caffeine or mock control. In addition, adenosine was used as a competitive inhibitor of caffeine. After 48 h, expression of IFN-γ and interleukin-17 (IL-17) was analysed by flow cytometry. Ex vivo expression levels of adenosine receptor A2a were also assessed. RESULTS: Caffeine promoted IFN-γ production in Th1 cells in vitro. Significantly higher concentrations of caffeine were required to increase IFN-γ levels in Th1 cells from healthy individuals compared to Th1 cells from patients with RA. Moreover, ex vivo levels of adenosine receptor A2a expression on CD4+ T cells were significantly higher in RA than in healthy individuals. Caffeine-driven IFN-γ production was completely reversed by adenosine, a competitive agonist of adenosine receptor A2a. In contrast to IFN-γ, production of IL-17 was not affected by caffeine. CONCLUSION: Caffeine promotes IFN-γ production in Th1 cells from RA patients in vitro by competitive inhibition of adenosine receptor A2a. Excessive coffee consumption could contribute to T-cell activation and inflammation in RA.