Caffeine suppresses TNF-alpha production via activation of the cyclic AMP/protein kinase A pathway. Export

@article{citeulike:4252573, abstract = {This study investigated the effect of in vitro exposure to caffeine, and its major metabolite paraxanthine, at concentrations relevant to typical caffeine consumption in humans, on lipopolysaccharide (LPS)-stimulated cytokine production in human whole blood. In addition, a role for the cyclic AMP/protein kinase A (PKA) pathway in the immunomodulatory effect of caffeine was investigated. Diluted whole blood (taken following >/=15 h abstinence from caffeine-containing food and beverages) was preincubated with caffeine or paraxanthine (10-100 microM) and stimulated with LPS (1 proportional, variant g/ml) for 24 h. The proinflammatory cytokines tumour necrosis factor (TNF)-alpha, interleukin (IL)-1beta and IL-12, and the antiinflammatory cytokine IL-10 were measured in cell-free supernatants. Whilst caffeine and paraxanthine had little or no effect on IL-10, IL-1beta, or IL-12 production, TNF-alpha production was suppressed in all individuals studied. The effect was statistically significant at 100 microM and consistent across seven experiments performed. Although not statistically significant, a similar effect was observed with paraxanthine. Caffeine (100 microM) also increased intracellular cyclic AMP concentrations in LPS-stimulated monocytes isolated from whole blood. Moreover, the effect of caffeine on TNF-alpha production was abolished by pretreatment with the protein kinase A inhibitor Rp-8-Br-cAMPS (10(-4) and 10(-5)M). To conclude, this study demonstrates that concentrations of caffeine that are relevant to human consumption consistently suppress production of the proinflammatory cytokine TNF-alpha in human blood and that this effect is mediated by the cyclic AMP/protein kinase A pathway.}, author = {Horrigan, L. A. and Kelly, J. P. and Connor, T. J.}, citeulike-article-id = {4252573}, citeulike-linkout-0 = {http://dx.doi.org/10.1016/j.intimp.2004.06.005}, citeulike-linkout-1 = {http://view.ncbi.nlm.nih.gov/pubmed/15313438}, citeulike-linkout-2 = {http://www.hubmed.org/display.cgi?uids=15313438}, doi = {10.1016/j.intimp.2004.06.005}, issn = {1567-5769}, journal = {International immunopharmacology}, keywords = {caffeine, camp, tnf-a}, month = {October}, number = {10-11}, pages = {1409--1417}, posted-at = {2009-04-01 11:44:35}, priority = {3}, title = {Caffeine suppresses TNF-alpha production via activation of the cyclic AMP/protein kinase A pathway.}, url = {http://dx.doi.org/10.1016/j.intimp.2004.06.005}, volume = {4}, year = {2004} }

TY - JOUR ID - citeulike:4252573 L3 - citeulike-article-id:4252573 N2 - This study investigated the effect of in vitro exposure to caffeine, and its major metabolite paraxanthine, at concentrations relevant to typical caffeine consumption in humans, on lipopolysaccharide (LPS)-stimulated cytokine production in human whole blood. In addition, a role for the cyclic AMP/protein kinase A (PKA) pathway in the immunomodulatory effect of caffeine was investigated. Diluted whole blood (taken following >/=15 h abstinence from caffeine-containing food and beverages) was preincubated with caffeine or paraxanthine (10-100 microM) and stimulated with LPS (1 proportional, variant g/ml) for 24 h. The proinflammatory cytokines tumour necrosis factor (TNF)-alpha, interleukin (IL)-1beta and IL-12, and the antiinflammatory cytokine IL-10 were measured in cell-free supernatants. Whilst caffeine and paraxanthine had little or no effect on IL-10, IL-1beta, or IL-12 production, TNF-alpha production was suppressed in all individuals studied. The effect was statistically significant at 100 microM and consistent across seven experiments performed. Although not statistically significant, a similar effect was observed with paraxanthine. Caffeine (100 microM) also increased intracellular cyclic AMP concentrations in LPS-stimulated monocytes isolated from whole blood. Moreover, the effect of caffeine on TNF-alpha production was abolished by pretreatment with the protein kinase A inhibitor Rp-8-Br-cAMPS (10(-4) and 10(-5)M). To conclude, this study demonstrates that concentrations of caffeine that are relevant to human consumption consistently suppress production of the proinflammatory cytokine TNF-alpha in human blood and that this effect is mediated by the cyclic AMP/protein kinase A pathway. IS - 10-11 JF - International immunopharmacology SN - 1567-5769 EP - 1417 TI - Caffeine suppresses TNF-alpha production via activation of the cyclic AMP/protein kinase A pathway. VL - 4 SP - 1409 KW - caffeine KW - camp KW - tnf-a AU - Horrigan, LA AU - Kelly, JP AU - Connor, TJ PY - 2004/10// UR - http://dx.doi.org/10.1016/j.intimp.2004.06.005 ER -