Simvastatin Reduces Burn Injury-induced Splenic Apoptosis via Downregulation of the TNF-α/NF-κB Pathway

Authors:
  • YYYong-Ming Yu
    Yong-Ming Yu
  • MKMasao Kaneki
    Masao Kaneki
  • ABAli A. Bonab
    Ali A. Bonab
  • RTRonald G. Tompkins
    Ronald G. Tompkins
  • AFAlan J. Fischman
    Alan J. Fischman
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Abstract
Objective: 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. Methods: 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. Results: 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. Conclusions: Simvastatin reduces burn-induced splenic apoptosis via downregulation of the TNF-α/NF-κB pathway.

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