Abstract
PurposeUnbalanced inflammatory response and lymphocyte apoptosis is associated with high mortality in septic patients. Decoy receptor 3 (DcR3), a member of the tumor necrosis factor receptor superfamily, is an anti-inflammatory and anti-apoptotic factor. Recently, DcR3 expression was found to be increased in septic patients. This study evaluated the therapeutic effect and mechanisms of DcR3 on cecal ligation and puncture (CLP)-induced sepsis in mice.MethodsC57BL/6 mice were subjected to CLP-induced polymicrobial sepsis. DcR3 Fc was intravenously injected 30 min before and 6 h after CLP. Bacterial clearance, cytokine production, histology, lymphocyte apoptosis and survival were evaluated. Furthermore, we investigated the systemic effects of DcR3 in in vitro lymphocyte apoptosis regulation.ResultsOur results demonstrated that DcR3 protein treatments significantly improved survival in septic mice (p <0.05). Treatment with DcR3 protein significantly reduced the inflammatory response and decreased lymphocyte apoptosis in the thymus and spleen. Histopathological findings of the lung and liver showed milder impairment after DcR3 administration. In vitro experiments showed that DcR3 Fc inhibited Fas-FasL mediated lymphocyte apoptosis.ConclusionsTreatment with the DcR3 protein protects mice from sepsis by suppressing the inflammatory response and lymphocyte apoptosis. DcR3 protein may be useful in treatment of sepsis.
Highlights
Despite advances in supportive care, sepsis remains one of the most challenging clinical problems due to its high morbidity and mortality in children and adults [1, 2]
Our results demonstrated that Decoy receptor 3 (DcR3) protein treatments significantly improved survival in septic mice (p
In order to investigate whether DcR3 was beneficial for cecal ligation and puncture (CLP) mice, survival were observed for 7 d after surgery
Summary
Despite advances in supportive care, sepsis remains one of the most challenging clinical problems due to its high morbidity and mortality in children and adults [1, 2]. The pathophysiological process of sepsis is a complex immunologic response with pro-inflammatory and antiinflammatory mechanisms alternatively predominating [3]. Recent studies have found that most patients survive the initial pro-inflammatory state but tend to die during the immunosuppression period [5]. Temporary immunosuppression during sepsis appears to be closely correlated with mortality and secondary infection [6]. Apoptotic cell uptake by phagocytic cells such as macrophages and dendritic cells (DCs) leads to an immunosuppressive state by inducing the production of anti-inflammatory cytokines and suppressing the release of pro-inflammatory cytokines [9, 10]. New drugs with effective anti-inflammatory profiles as well as immunomodulatory properties would be promising and valuable
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