1. Probenecid reduces infection and inflammation in acute Pseudomonas aeruginosa pneumonia.
- Author
-
Wonnenberg B, Tschernig T, Voss M, Bischoff M, Meier C, Schirmer SH, Langer F, Bals R, and Beisswenger C
- Subjects
- Animals, Cell Line, Cytokines metabolism, Disease Models, Animal, Humans, Inflammation pathology, Mice, Inbred C57BL, Pneumonia, Bacterial pathology, Pseudomonas Infections pathology, Anti-Inflammatory Agents therapeutic use, Inflammation prevention & control, Pneumonia, Bacterial prevention & control, Probenecid therapeutic use, Pseudomonas Infections prevention & control, Pseudomonas aeruginosa isolation & purification, Uricosuric Agents therapeutic use
- Abstract
The activation of inflammasome signaling mediates pathology of acute Pseudomonas aeruginosa pneumonia. This suggests that the inflammasome might represent a target to limit the pathological consequences of acute P. aeruginosa lung infection. Pannexin-1 (Px1) channels mediate the activation of caspase-1 and release of IL-1β induced by P2X7 receptor activation. The approved drug probenecid is an inhibitor of Px1 and ATP release. In this study, we demonstrate that probenecid reduces infection and inflammation in acute P. aeruginosa pneumonia. 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. In addition, probenecid inhibited the release of inflammatory mediators in murine alveolar macrophages and human U937 cell-derived macrophages upon bacterial infection but not in human bronchial epithelial cells. Thus, Px1 blockade via probenecid treatment may be a therapeutic option in P. aeruginosa pneumonia by improving bacterial clearance and reducing negative consequences of inflammation., (Copyright © 2014 Elsevier GmbH. All rights reserved.)
- Published
- 2014
- Full Text
- View/download PDF