HMG-CoA reductase inhibitor simvastatin improves organ dysfunction, inflammatory profile, bacterial clearance and cognitive damage after onset of sepsis
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1
Fundação Oswaldo Cruz, Brazil
Sepsis is a clinical syndrome characterized by systemic inflammatory response secondary to infection, which can progress to multiple organ dysfunction and death. Cognitive impairment is a significant consequence of sepsis reported among survivors. Despite research on new therapies, sepsis treatment remains based on life support and antibiotics. Cohort studies have suggested that statin uses are associated with protection from development and mortality of sepsis. Statins have pleiotropic effects and they are emerging as potent inhibitors of inflammatory processes. In this study we aimed to evaluate the effects of simvastatin in a clinical relevant model of sepsis in rodents (Cecal Ligation and Puncture-CLP). Swiss Webster mice were submitted to CLP and 6h later they were treated with simvastatin (2mg/kg – iv). Plasma and peritoneal lavage were collected for organ damage evaluation, cytokine (ELISA) and nitric oxide (NO) (Griess method) quantification, cell migration and bacterial clearance (colony forming units-CFU) analysis. Cognitive damage was evaluated through inhibitory avoidance task. Our results showed that simvastatin decreased liver and kidney damage, and significantly reduced neutrophils numbers, CFU counts, TNF, MIF, IL-6 and IL1 levels in the peritoneum. Simvastatin decreased NO levels in the bloodstream, but it enhanced NO production in the peritoneum. Additionally, simvastatin prevented the loss of aversive memory in septic mice. Our study demonstrates that simvastatin improved inflammatory profile and bacterial elimination in sepsis, preventing organ dysfunction and late consequences of sepsis. Our study indicates that statins can be considered potential candidate to future clinical studies as adjuvant therapy for sepsis.
Acknowledgements
Financial Support: CNPq, FAPERJ, FIOCRUZ
References
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Keywords:
Sepsis,
Statins,
clp,
Nitric Oxide,
HMG-CoA reductase
Conference:
15th International Congress of Immunology (ICI), Milan, Italy, 22 Aug - 27 Aug, 2013.
Presentation Type:
Abstract
Topic:
Innate immunity
Citation:
Magno
F,
Gonçalves-de-Albuquerque
CF,
Medeiros-de-Moraes
IM,
Reis
PA,
Bozza
PT,
Bozza
FA,
Silva
AR and
Castro-Faria-Neto
HC
(2013). HMG-CoA reductase inhibitor simvastatin improves organ dysfunction, inflammatory profile, bacterial clearance and cognitive damage after onset of sepsis.
Front. Immunol.
Conference Abstract:
15th International Congress of Immunology (ICI).
doi: 10.3389/conf.fimmu.2013.02.01148
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Received:
31 Jul 2013;
Published Online:
22 Aug 2013.
*
Correspondence:
Miss. Flora Magno, Fundação Oswaldo Cruz, Rio de Janeiro, Rio de Janeiro, 21040-900, Brazil, floramag@gmail.com