Comparing the anti-inflammatory effects of Simvastatin and Rosuvastatin by measuring IL-1β, IL-6 and TNF-α levels using a murinic caecal ligation and puncture induced sepsis model / Compararea efectelor anti-inflamatoare ale Simvastatinei și Rosuvastatinei măsurând nivelele serice ale IL-1β, IL-6 si TNF-α folosind un model de sepsis la șobolan indus prin ligatură și puncție cecală

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Abstract

Background: Sepsis is a systemic host response to an infection which may evolve into severe sepsis and septic shock. It raises many health care related concerns around the world, carrying almost 30% mortality rates and a high financial burden. The disease is characterized by the triggering of some inflammatory pathways that are ultimately proven deleterious to the host organism. Although antibiotics, fluid administration, vasopressor therapy and infectious source control remain the recommended management strategies, emerging scientific data proposes statins as a new line of treatment. These drugs were first introduced in clinical practice for their cholesterol-lowering effect but the inhibition of HMG-CoA reductase and cholesterol biosynthetic pathway exhibits some less studied effects generally referred to as pleiotropic: anti-inflammatory, antithrombotic, immunomodulatory and antioxidant properties. Objective: To asses and compare the anti-inflammatory effect of two statins - Simvastatin and Rosuvastatin - measuring blood levels of IL-1β, IL-6 and TNFα using a previously described murinic model of sepsis. Methods: We compiled four groups (C, n=7; SEP, SV, RV, n=8). Statins were administered in two doses 18 and 3 hours before surgical intervention. Sepsis was induced using the caecal ligation and puncture technique. Blood samples were obtained by venepuncture from each subject in day 1, 4, 7 and 14 (the last samples were obtained by cardiac puncture). Complete blood count, Procalcitonin, IL-1β, IL-6 and TNF-α levels were assessed. Results: White blood cell counts differed across the groups showing a higher count for the septic but untreated group. Procalcitonin reacted in all septic groups but both statin treated groups had lower levels when compared to untreated group. IL-1β levels were higher in the Rosuvastatin treated group. IL-6 levels were more heterogeneously dispersed but higher levels were noticed in the untreated septic group. The Simvastatin treated group had higher levels compared to the Rosuvastatin treated one. TNFα levels were higher in the septic untreated group and in the Rosuvastatin treated one. For the Simvastatin treated subjects, the level of TNFα was similar with the control group. Conclusion: We concluded that both drugs showed anti-inflammatory effects on the murinic CLP-induced sepsis model. Between the two, Simvastatin had greater impact by lowering blood levels of established pro-inflammatory markers.

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