Novel Insights into Beneficial Consequences of Statins in Sepsis: Anti-inflammatory and Anti-apoptotic Mechanisms

Sepsis represents an important health care problem and remains the leading cause of death in intensive care units. A major problem leading to the high morbidity and high mortality of this nasty illness is the lack of effective medical treatment. There is evidence from animal studies and observational clinical studies that statin treatment may be beneficial in sepsis. We assessed whether treatment with pitavastatin, a new synthetic statin with highly potent and efficacious HMG-CoA reductase inhibition, can reduce the development of acute lung injury (ALI) and improve survival in mice with cecal ligation and puncture (CLP)-induced polymicrobial sepsis. We observed that treatment with pitavastatin efficiently prevented the ALI development in CLP mice. This was associated with down-regulated NF- B activation as a consequence of the up-regulation of glucocorticoid receptor expression, which stemmed from the increased number of alveolar macrophages. In addition, the anti-apoptotic action of pitavastatin was involved in its survival benefit in CLP mice. Our results could provide some rationale for statin use in sepsis as a potentially significant benefit.