Simvastatin Reduces Burn Injury-induced Splenic Apoptosis via Downregulation of the TNF-α/NF-κB Pathway. Issue 5 (May 2015)

• Record Type: Journal Article
• Authors: Zhao, Gaofeng; Yu, Yong-Ming; Kaneki, Masao; Bonab, Ali A.; Tompkins, Ronald G.; Fischman, Alan J.
• Is Part Of: Annals of surgery. Volume 261:Issue 5(2015:May)
• Publication Date: 2015-05
• Subjects: Surgery -- Periodicals; 617.005
• DOI: 10.1097/SLA.0000000000000764
• Languages: English
• ISSNs: 0003-4932

Abstract

<abstract> <title> <x xml:space="preserve">Abstract</x> </title> <sec> <title>Objective:</title> <p>Recent studies have suggested that epidermal burn injuries are associated with inflammation and immune dysfunction. Simvastatin has been shown to possess potent anti-inflammatory properties. Thus, we hypothesized that simvastatin protects against burn-induced apoptosis in the spleen via its anti-inflammatory activity.</p> </sec> <sec> <title>Methods:</title> <p>Wild-type, tumor necrosis factor alpha knockout (TNF-α KO) and NF-κB KO mice were subjected to full-thickness burn injury or sham treatment. The mice then were treated with or without simvastatin, and the spleen was harvested to measure the extent of apoptosis. Expression levels of TNF-α and NF-κB were also determined in spleen tissue and serum.</p> </sec> <sec> <title>Results:</title> <p>Burn injury induced significant splenic apoptosis and systemic cytokine production. Simvastatin protected the spleen from apoptosis, reduced cytokine production in the serum, and increased the survival rate. Simvastatin decreased burn-induced TNF-α and NF-κB expression in the spleen and serum. TNF-α and NF-κB KO mice demonstrated lower levels of apoptosis in spleen in response to burn injury. Simvastatin did not further decrease burn-caused apoptosis and mortality in either strain of KO mice.</p> </sec> <sec> <title>Conclusions:</title> <p>Simvastatin reduces burn-induced splenic apoptosis via downregulation of the TNF-α/NF-κB pathway.</p> </sec> </abstract>