Immunoregulatory effects of adenosine 5′‐triphosphate on cytokine release from stimulated whole blood

Publisher Website
Google Scholar
Abstract
In vitro studies suggest that extracellular nucleotides and nucleosides may be important regulators of inflammatory and immune responses. Most studies with adenosine 5′-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 TNF-α, 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 μM and 300 μM induced a reduction in TNF-α secretion by 32±8% (mean ± SEM) and 65±4%, respectively. Furthermore, these ATP concentrations induced an increase in IL-10 secretion by 48±5% and 62±7% in whole blood. The ATP analogue adenosine 5′-O-(3-thiotriphosphate) (ATP-γ-S) and adenosine 5′-diphosphate (ADP) also inhibited TNF-α release, but only ADP showed a stimulatory effect on IL-10. Co-treatment with adenosine deaminase did not reverse the ATP effect on TNF-α 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-α and stimulation of IL-10 release and that this effect is predominantly mediated by ATP and not by adenosine.