title: Simvastatin reduces burn injury-induced splenic apoptosis via downregulation of the TNF-α/NF-κB pathway.
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.
authors.affiliation: From the Surgical Service, Massachusetts General Hospital, Shriners Hospitals for Children, and Harvard Medical School, Boston, MA.
authors.forename: Gaofeng
authors.initials: G
authors.lastname: Zhao
authors.forename: Yong-Ming
authors.initials: YM
authors.lastname: Yu
authors.forename: Masao
authors.initials: M
authors.lastname: Kaneki
authors.forename: Ali A
authors.initials: AA
authors.lastname: Bonab
authors.forename: Ronald G
authors.initials: RG
authors.lastname: Tompkins
authors.forename: Alan J
authors.initials: AJ
authors.lastname: Fischman
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology* / Q000627:therapeutic use; D017209:Apoptosis / Q000187:drug effects*; D002056:Burns / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D016207:Cytokines / Q000097:blood; D015536:Down-Regulation; D018345:Mice, Knockout; D016328:NF-kappa B / Q000097:blood / Q000378:metabolism*; D019821:Simvastatin / Q000494:pharmacology* / Q000627:therapeutic use; D013154:Spleen / Q000473:pathology*; D014409:Tumor Necrosis Factor-alpha / Q000097:blood / Q000378:metabolism*
chemical_list: D000893:Anti-Inflammatory Agents; D016207:Cytokines; D016328:NF-kappa B; D014409:Tumor Necrosis Factor-alpha; D019821:Simvastatin