Do statins have a role in preventing or treating sepsis?

Severe sepsis is an infection-induced inflammatory syndrome that ultimately leads to organ dysfunction. It is estimated that more than 500,000 episodes of sepsis occur each year in the USA alone, and that 20–50% of these patients will die [1]. Disturbingly, the incidence of sepsis and number of sepsis-related deaths appear to be increasing [1]. Important progress has been made in recent years, and interventions such as activated protein C, early goal-directed therapy, and possibly low-dose corticosteroids have been shown to improve survival in patients with severe sepsis [2]. Despite these advances, mortality remains unacceptably high and care for patients with sepsis costs as much as $50,000 per patient, resulting in an economic burden of nearly $17 billion annually in the USA alone [1].It is generally accepted that sepsis syndrome reflects the delicate balance between extensive triggering of defense mechanisms by invading micro-organisms and both direct and indirect effects of these micro-organisms and their products. Most investigators would agree that severe sepsis is accompanied by the inability to regulate the inflammatory response and that the cause of this perturbation is still not well defined [2]. In fact, Sir William Osler, some 100 years ago, suggested that, 'Except on few occasions the patient appears to die from the body's response to infection rather than from it' [3]. Over the past 3 decades, numerous trials have failed to demonstrate that blocking specific inflammatory mediators is beneficial in sepsis. Despite this frustration, new strategies are being explored such as blockade of high-mobility group B1 protein, macrophage migration inhibitory factor, and the complement split product C5a [2]. However, in complex situations such as severe sepsis, multiple cellular activation processes are involved and many humoral cascades are triggered, and so merely blocking a single component may be insufficient to arrest the inflammatory process [4]. Given the a