Adenosine and interferon alpha synergistically increase IFN-gamma production of PBMC via the A3-receptor

Prevention of overwhelming immune reactions is essential for an organism to survive. Adenosine, a ribonucleoside displaying multiple functions in various tissues and produced by different cell types during inflammatory processes, has been shown to inhibit effector functions of different immune cells. Here we show that adenosine very potently inhibited proliferation, IFN- gamma production and cytotoxicity of activated human lymphoid cells via the A3-receptor. Stimulation of the A3-receptor also caused apoptosis of activated PBMC. Surprisingly, interferon alpha and adenosine synergistically increased interferon gamma production of PBMC in healthy subjects as well as in individuals infected with HBV and HCV and in patients during antiviral therapy with pegylated interferon alpha. Thus, our data suggest that adenosine and interferon alpha may synergistically increase effector functions during acute infections but also prevent overwhelming immune responses by inhibiting proliferation and induction of apoptosis of activated lymphoid cells. The role of adenosine for treatment response in interferon alpha-based antiviral therapy in viral hepatitis requires further investigation.