Journal Article

Resolvin D1 improves survival in experimental sepsis through reducing bacterial load and preventing excessive activation of inflammatory response

Bao, R., Wu, Y. P., Fan, X. H., Li, J. B., Bo, L. L., Chen, F., Wang, F., Deng, X. M., Zhu, J. L.

2014

Overview

Sepsis is characterized as an uncontrolled inflammatory response. Spite et al. (Nature 461(7268):1287–1291, 2009 ) had demonstrated that resolvin D2, which is derived from docosahexaenoic acid (DHA), improves survival in cecal ligation and puncture (CLP)-initiated sepsis and enhances bacterial clearance without immune suppression. Resolvin D1, which is also derived from DHA and homologous with resolvin D2, is an endogenous anti-inflammatory and proresolving lipid molecule. We sought to investigate the effects of resolvin D1 on sepsis and to explore the mechanism of action. Six-to-eight-week-old male C57BL/6 mice were randomly divided into three groups: the sham group underwent the sham operation followed by tail vein injection of vehicle (0.1 % ethanol); the CLP group received vehicle (0.1 % ethanol) after CLP; the resolvin D1 group received resolvin D1 (100 ng) after CLP. Blood, peritoneal lavage fluid, and organs of mice were harvested 24 h after treatment for cytokine analysis, cell counts, bacterial cultures, histopathological studies, and apoptosis quantification. Compared with the vehicle control group, the survival rate and bacterial clearance of mice with sepsis induced by CLP were improved after resolvin D1 treatment, but the numbers of neutrophils in peritoneal lavage fluid, the inflammatory cytokines, the phosphorylation of the nuclear factor-κB (NF-κB) (P65) pathway, and the apoptosis rate of CD3 +  T lymphocytes of the thymus were suppressed. Resolvin D1 treatment improved survival in mice with sepsis induced by CLP, enhanced organism bacterial clearance, suppressed the increase of the numbers of neutrophils in peritoneal lavage fluid, reduced the release of inflammatory cytokines, and decreased the apoptosis rate of CD3 +  T lymphocytes of the thymus. These results suggest that resolvin D1 may attenuate the degree of inflammatory reaction in sepsis caused by CLP, without harming the host defense response.

• Publisher: Springer Berlin Heidelberg,Springer,Springer Nature B.V
• Subject: Abdomen / Animals / Apoptosis / Apoptosis - drug effects / Bacteria / Bacterial diseases / Bacterial Load - drug effects / Bacterial sepsis / Biological and medical sciences / Biomedical and Life Sciences / Biomedicine / Cytokines / Cytokines - blood / Disease Models, Animal / Docosahexaenoic Acids - pharmacology / Ethanol / Fatty acids / Human bacterial diseases / Infectious diseases / Inflammation / Inflammation - metabolism / Inflammation - microbiology / Inflammation - pathology / Inflammation - prevention & control / Internal Medicine / Kaplan-Meier Estimate / Leukocytes / Lipids / Lung - drug effects / Lung - metabolism / Lymphocytes / Male / Medical Microbiology / Medical prognosis / Medical sciences / Mice / Mice, Inbred C57BL / Neutrophils / NF-kappa B - metabolism / Pathogenesis / Random Allocation / Sepsis / Sepsis - drug therapy / Sepsis - metabolism / Sepsis - microbiology / Sepsis - pathology / Survival / Thymus gland / Tumor necrosis factor-TNF