Glatiramer acetate treatment inhibits inflammatory responses and improves survival in a mice model of cecal ligation and puncture-induced sepsis
Author:
Maleki Elahe1, Sheibani Mohammad23, Nezamoleslami Sadaf23, Dehpour Ahmad Reza23, Takzaree Nasrin4, Shafaroodi Hamed23ORCID
Affiliation:
1. Faculty of Pharmacy and Pharmaceutical Science, Islamic Azad University of Medical Science , Tehran , Iran 2. Department of Pharmacology , School of Medicine, Tehran University of Medical Sciences , Tehran , Iran 3. Experimental Medicine Research Center, Tehran University of Medical Sciences , Tehran , Iran 4. Department of Anatomy & Histology , School of Medicine, Tehran University of Medical Science , Tehran , Iran
Abstract
Abstract
Objectives
Sepsis is a clinical crisis which has been considered as one of the important causes of mortality across the world. We hypothesized that modulation of hyper-inflammatory phase of sepsis pathophysiology can lead to protective effects on survival outcome. Glatiramer acetate (GA) is a neuroprotective drug commonly used in multiple sclerosis (MS). GA is characterized by immunom activity via regulation of innate and adaptive immunity. This study was designed to evaluate the acute treatment with GA on initial inflammatory response-induced mortality in septic mice.
Methods
Cecal ligation and puncture (CLP) model was operated on male mice as a model of Polymicrobial sepsis. GA was administrated intraperitoneally after the sepsis induction at doses of 0.5, 1, and 2 mg/kg in three treatment groups. To investigate the effect of GA on short-term survival, septic mice were observed during 72 h after CLP. Serum levels of TNF-α, IL-1β, and IL-6 as pro-inflammatory cytokines and also IL-10 as a critical anti-inflammatory cytokine were analysed. To consider sepsis-induced acute kidney injury, renal functional biomarkers and histopathological changes was assessed.
Results
GA treatment significantly improved survival rate at doses of 1, and 2 mg/kg. Survival improvement was accompanied by remarkable reduction in the pro-inflammatory cytokines and enhanced production of IL-10. GA showed to have protective effects on renal function as well.
Conclusions
Immunomodulatory and anti-inflammatory properties of GA resulted in increase in survival rate and decrease in inflammatory markers in mice model of cecal ligation and puncture–induced sepsis.
Publisher
Walter de Gruyter GmbH
Subject
Drug Discovery,Pharmacology,General Medicine,Physiology
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