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Shock 2011 Apr;35(4):38

Adenosine Negative Feedback On A2A Adenosine Receptors Mediates Hypo-Responsiveness In Chronically Septic Mice

Belikoff, B; Hatfield, S; Remick, DG.; Sitkovsky, M

Department of Pathology and Laboratory Medicine, Boston University School of Medicine, Boston, MA, USA.

Strategies are needed to reverse the immune cell hyporesponsiveness and prevent bacterial overgrowth associated with high mortality rates in septic patients. Adenosine signaling may be mediating immunosuppressive signals within the inflammatory microenvironment that are safeguarding bacteria by rendering immune cells hyporesponsive. We examined A2A adenosine receptor (A2AR)-mediated immune responses in a chronic model of cecal ligation and puncture (CLP)-induced sepsis using both wild-type (WT) and A2AR knockout (KO) mice. In this model, chronic bacterial peritonitis was established that results in the first death on day 4. A2A adenosine receptors promoted bacterial overgrowth that was associated with a high 28-day sepsis mortality (WT 87% vs. A2AR KO 13%; Pccharide (day 5 after CLP) challenge, A2AR KO mice showed enhanced secretion of TNF- (2 h), IFN- , IL-6, monocyte chemotactic protein 1, IL-10, and macrophage inflammatory protein 2 (9 h) (Pbacterial overgrowth and reduce mortality secondary to immunosuppression in septic patients.

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