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

In Brief 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. We found burn-induced splenic apoptosis. Simvastatin reduced the apoptosis, TNF-α, and NF-κB expressions. TNF-α and NF-κB knockout (KO) mice demonstrated lower levels of apoptosis. Simvastatin did not decrease apoptosis in the KO mice. We concluded that simvastatin reduces burn-induced splenic apoptosis via downregulation of TNF-α/NF-κB.