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Mediators of Inflammation
Volume 2013, Article ID 503213, 9 pages
Research Article

NF- B Inhibition after Cecal Ligation and Puncture Reduces Sepsis-Associated Lung Injury without Altering Bacterial Host Defense

1Division of Respiratory Medicine, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, Guangdong Province 510080, China
2Department of Cancer Biology, Vanderbilt University School of Medicine, Nashville, TN 37232, USA
3Division of Respiratory Medicine, Nanjing Drum Tower Hospital & the Affiliated Hospital of Nanjing University, Nanjing, Jiangsu 210008, China
4Department of Medicine, Division of Allergy, Pulmonary and Critical Care Medicine, Vanderbilt University School of Medicine, Nashville, TN 37232, USA
5Departments of Medicine and Immunology, Roswell Park Cancer Institute, Buffalo, NY 14263, USA
6Department of Medicine, School of Medicine and Biomedical Sciences, University of New York at Buffalo, Buffalo, NY 14214, USA
7Department of Cell and Developmental Biology, Vanderbilt University School of Medicine, Nashville, TN 37232, USA
8Department of Veterans Affairs Medical Center, Nashville, TN 37232, USA

Received 28 June 2013; Revised 17 August 2013; Accepted 10 October 2013

Academic Editor: Philipp Lepper

Copyright © 2013 Hui Li et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


Introduction. Since the NF- B pathway regulates both inflammation and host defense, it is uncertain whether interventions targeting NF- B would be beneficial in sepsis. Based on the kinetics of the innate immune response, we postulated that selective NF- B inhibition during a defined time period after the onset of sepsis would reduce acute lung injury without compromising bacterial host defense. Methods. Mice underwent cecal ligation and puncture (CLP). An NF- B inhibitor, BMS-345541 (50 µg/g mice), was administered by peroral gavage beginning 2 hours after CLP and repeated at 6 hour intervals for 2 additional doses. Results. Mice treated with BMS-345541 after CLP showed reduced neutrophilic alveolitis and lower levels of KC in bronchoalveolar lavage fluid compared to mice treated with CLP+vehicle. In addition, mice treated with CLP+BMS had minimal histological evidence of lung injury and normal wet-dry ratios, indicating protection from acute lung injury. Treatment with the NF- B inhibitor did not affect the ability of cultured macrophages to phagocytose bacteria and did not alter bacterial colony counts in blood, lung tissue, or peritoneal fluid at 24 hours after CLP. While BMS-345541 treatment did not alter mortality after CLP, our results showed a trend towards improved survival. Conclusion. Transiently blocking NF- B activity after the onset of CLP-induced sepsis can effectively reduce acute lung injury in mice without compromising bacterial host defense or survival after CLP.