Modulation of innate immunity by adenosine receptor stimulation.

In the past decades, increased concentrations of the signaling molecule adenosine have been shown to play an important role in the prevention of tissue damage evoked by several stressful circumstances. During systemic inflammation, the circulating adenosine concentration increases rapidly, even up to 10-fold in septic shock patients. By binding to specific adenosine receptor subtypes, designated A1, A2a, A2b, and A3, adenosine exerts a wide variety of immunomodulating and (cyto)protective effects. Only recently, several specific adenosine receptor agonists and other drugs that modulate adenosine metabolism have been developed for human use. Importantly, correct interpretation of the effects of adenosine is highly related to the model of inflammation used, e.g., administration of endotoxin or live bacteria. This review will discuss the potential role for adenosine as an immunomodulating and cytoprotective signaling molecule and will discuss its potential role in the treatment of the patient suffering from sepsis.