Arezou Khosrojerdi1, Sara Soudi2, Ahmad Zavaran Hosseini1, Sahar Ghaffari Khaligh3, Seyed Mahmoud Hashemi4. 1. Department of Immunology, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran. 2. Department of Immunology, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran. Electronic address: soudi@modares.ac.ir. 3. Department of Pathology, Faculty of Veterinary Medicine, Semnan University, Semnan, Iran. 4. Department of Immunology, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
Abstract
BACKGROUND: Considering the role of inflammation in the outcome of sepsis and the widespread use of imipenem in the disease, this study was designed to assess the effect of imipenem on the dynamics of inflammatory responses in the sepsis mouse model. METHODS: Cecal Ligation and Puncture (CLP) model was used to induce sepsis in mice. C57BL/6 mice were divided into sham, CLP-induced sepsis mice, CLP-induced sepsis mice receiving 25 mg/kg, and 125 mg/kg imipenem. Blood and liver samples were obtained and bacterial load, endotoxin level, and liver enzymes were evaluated. The concentration and mRNA expression of cytokines were also determined. RESULTS: Sepsis mice treated with a high dose (125 mg/kg) of imipenem showed a significant reduction in bacterial load, while increased liver enzymes, endotoxin level, and inflammatory cytokine production in plasma and liver. In contrast, significant reduction in the liver enzymes, bacterial load, endotoxin levels, and inflammatory cytokine levels was observed in the mice treated with a low dose (25 mg/kg) of imipenem compared with other mice groups. Liver tissue pathology of mice indicated little tissue destruction in the sepsis mice treated with 25 mg/kg of imipenem compared to other groups. Mice receiving 25 mg/kg of imipenem had better survival rate. CONCLUSIONS: Our results demonstrated the dose-dependent effect of subcutaneous administration of imipenem on the inflammatory responses in sepsis mice. A dose of 25 mg/kg imipenem resulted in better pathology, lower inflammatory mediators, and increased survival rate in sepsis mice.
BACKGROUND: Considering the role of inflammation in the outcome of sepsis and the widespread use of imipenem in the disease, this study was designed to assess the effect of imipenem on the dynamics of inflammatory responses in the sepsismouse model. METHODS: Cecal Ligation and Puncture (CLP) model was used to induce sepsis in mice. C57BL/6 mice were divided into sham, CLP-induced sepsismice, CLP-induced sepsismice receiving 25 mg/kg, and 125 mg/kg imipenem. Blood and liver samples were obtained and bacterial load, endotoxin level, and liver enzymes were evaluated. The concentration and mRNA expression of cytokines were also determined. RESULTS:Sepsismice treated with a high dose (125 mg/kg) of imipenem showed a significant reduction in bacterial load, while increased liver enzymes, endotoxin level, and inflammatory cytokine production in plasma and liver. In contrast, significant reduction in the liver enzymes, bacterial load, endotoxin levels, and inflammatory cytokine levels was observed in the mice treated with a low dose (25 mg/kg) of imipenem compared with other mice groups. Liver tissue pathology of mice indicated little tissue destruction in the sepsismice treated with 25 mg/kg of imipenem compared to other groups. Mice receiving 25 mg/kg of imipenem had better survival rate. CONCLUSIONS: Our results demonstrated the dose-dependent effect of subcutaneous administration of imipenem on the inflammatory responses in sepsismice. A dose of 25 mg/kg imipenem resulted in better pathology, lower inflammatory mediators, and increased survival rate in sepsismice.