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In vitro studies suggest that extracellular nucleotides and nucleosides may be important regulators of inflammatory and immune responses. Most studies with adenosine 5 0 -triphosphate (ATP) have been performed in cell lines, which are remote from the human situation. The purpose of the present study was to determine the effects of ATP on TNFa, IL-6 and IL-10 release in stimulated whole blood. Blood samples were drawn from healthy volunteers and incubated with ATP and lipopolysaccharide (LPS) + phytohemagglutinin (PHA) for 24 h. Contrary to expectations, ATP at 100 lM and 300 lM induced a reduction in TNF-a secretion by 32AE8% (mean AE SEM) and 65AE4%, respectively. Furthermore, these ATP concentrations induced an increase in IL-10 secretion by 48AE5% and 62AE7% in whole blood. The ATP analogue adenosine 5 0 -O-(3-thiotriphosphate) (ATP-c-S) and adenosine 5 0 -diphosphate (ADP) also inhibited TNF-a release, but only ADP showed a stimulatory effect on IL-10. Co-treatment with adenosine deaminase did not reverse the ATP effect on TNF-a and IL-10. These results show, for the first time, that ATP inhibits the inflammatory response in stimulated whole blood as indicated by inhibition of TNF-a and stimulation of IL-10 release and that this effect is predominantly mediated by ATP and not by adenosine.

The endogenous antioxidant defense was significantly reduced in sarcoidosis, indicating that oxidative stress underlies the pathology of this disease. Furthermore, the inflammatory status was significantly enhanced in sarcoidosis. Finally, our results regarding the effect of quercetin on cytokine production imply that sarcoidosis patients might benefit from antioxidant supplementation not only by empowering the relatively low protection against ROS but also by reducing inflammation.