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 spleen via its anti-inflammatory activity. Methods Wild-type, tumor necrosis factor alpha knockout (TNF-αKO) 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 were harvested to measure the extent of apoptosis. Expression levels of TNF-αand 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-αand NF-κB expression in spleen and serum. TNF-αand NF-κB KO mice demonstrated lower levels of apoptosis in spleen in response to burn. Simvastatin did not further decrease burn-caused apoptosis and mortality in either strain of KO mice. Conclusions Simvastatin reduces burn-induced splenic apoptosis via down-regulation of the TNF-α/ NF-κB pathway.

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