Anesthésie et recherche clinique
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HMG-CoA Reductase Inhibitors Decrease Hyperglycemia on Animal Model of Systemic Inflammatory Response Syndrome (SIRS)

Pinar Aksoy, Michael J. Brown and Eduardo N. Chini

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.