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: Gaofeng Zhao, Yong-Ming Yu, Masao Kaneki, Ali A Bonab, Ronald G Tompkins, Alan J Fischman
• Journal: Annals of surgery (Ann Surg) Vol. 261 Issue 5 Pg. 1006-12 (May 2015) ISSN: 1528-1140 [Electronic] United States
• PMID: 24950285 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Anti-Inflammatory Agents
• Cytokines
• NF-kappa B
• Tumor Necrosis Factor-alpha
• Simvastatin

Topics

• Animals
• Anti-Inflammatory Agents (pharmacology, therapeutic use)
• Apoptosis (drug effects)
• Burns (drug therapy, metabolism, pathology)
• Cytokines (blood)
• Down-Regulation
• Mice, Knockout
• NF-kappa B (blood, metabolism)
• Simvastatin (pharmacology, therapeutic use)
• Spleen (pathology)
• Tumor Necrosis Factor-alpha (blood, metabolism)