Abstract
Systemic Inflammatory Response Syndrome (SIRS) is a pathophysiologic state associated with trauma and major surgery. Inflammatory cytokines plays an important role in the pathogenesis of SIRS. Cytokines induce the activation of the classic hypothalamic-pituitary stress response that leads to increase of secretion of the stress hormone ACTH and hyperglycemia. HMG-CoA reductase inhibitors, such as statins, have been shown to have anti-inflammatory properties. Recent studies in humans indicate that the perioperative use of statins may decrease morbidity and mortality. Here we tested the hypothesis that statins may decrease the cytokine-induced stress response and hyperglycemia in a murine model of SIRS. SIRS was induced with intraperitoneal injection of 0.1 mg lipopolysaccharide (LPS) per mouse. Mice were pretreated with 0.5 mg of simvastatin or lovastatin 18 hours before the administration of LPS, and plasma levels of Interleukin-2 (IL-2), Tumor Necrosis Factor alpha (TNF-?), the stress hormone adrenocorticotrophic hormone (ACTH), and glucose were determined. We observed that pretreatment of mice with statins nearly completely suppressed the LPS-induced cytokine, ACTH and hyperglycemic responses. Conclusion: Statins suppress cytokine production in a murine model of SIRS. This decreased cytokine production may lead to suppression of the SIRS-induced stress response and hyperglycemia. We postulate that statins may have an important role as regulators of the SIRS and stress response induced by surgery and trauma, and that akin to ?-blockers, statins may become part of the therapeutic arsenal aimed to decrease perioperative morbidity and mortality.
Highlights
Systemic Inflammatory Response Syndrome (SIRS) is an often noted complication associated with trauma and major surgery [1,2,3]
SIRS is initiated by trauma that triggers an increase in pro-inflammatory cytokines, namely tumor necrosis alpha (TNFa), IL-2 and others (1-2)
We describe that the pre-treatment of mice with simvastatin can almost completely prevent the increase in adrenocorticotrophic hormone (ACTH) release after LPS treatment (Figure 2)
Summary
Systemic Inflammatory Response Syndrome (SIRS) is an often noted complication associated with trauma and major surgery [1,2,3]. It has been clearly shown that perioperative hyperglycemia increases morbidity and mortality in critically ill hospitalized patients, and initiating a practice of strict glycemic control is an important modality to reduce mortality in the ICU [6]. Stains are associated with decreased perioperative cardiovascular morbidity and mortality in vascular surgery patients [10,11,12]. The mechanism by which statins decrease perioperative mortality and improve survival in animal models of sepsis/SIRS is not completely understood. We postulate that statins may decrease perioperative morbidity and mortality at least in part by attenuating the inflammatory induced stress response and resultant hyperglycemia observed during and after surgical trauma
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