Blockade of Pannexin-1 (PX1) reduces inflammation and colonization in bacterial pneumonia

A recent paper has shown that the activation of inflammasome signaling mediates pathology of acute Pseudomonas aeruginosa pneumonia. The authors suggest the inflammasome as a target to limit the pathological consequences of acute P. aeruginosa lung infection. Pannexin-1 channels mediate activation of caspase-1 and release of IL-1β induced by P2X7 receptor activation. The approved drug probenecid is an inhibitor of pannexin-1 channels and ATP release. In this study, we demonstrate that probenecid reduces inflammation and colonization in bacterial lung infection. Probenecid treatment of mice prior to infection with P. aeruginosa resulted in an enhanced clearance of P. aeruginosa and reduced levels of inflammatory mediators, such as IL-1β. Probenecid inhibited the release of inflammatory mediators in human U937 cell-derived macrophages but not in bronchial epithelial cells upon bacterial infection. Thus, probenecid treatment may be therapeutic option in bacterial pneumonia by improving bacterial clearance and reducing pathological inflammation.