title: Decoy Receptor 3 Improves Survival in Experimental Sepsis by Suppressing the Inflammatory Response and Lymphocyte Apoptosis.
abstract: OBJECTIVE
  Unbalanced 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.
  
  
  METHODS
  C57BL/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.
  
  
  RESULTS
  Our 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.
  
  
  CONCLUSIONS
  Treatment 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.
authors.affiliation: Department of Central Laboratory, Songjiang Hospital Affiliated First People's Hospital, Shanghai Jiao Tong University, Shanghai, China.
authors.forename: DongYu
authors.initials: D
authors.lastname: Liang
authors.affiliation: Department of Central Laboratory, Songjiang Hospital Affiliated First People's Hospital, Shanghai Jiao Tong University, Shanghai, China.
authors.forename: YanQiang
authors.initials: Y
authors.lastname: Hou
authors.affiliation: Department of Central Laboratory, Songjiang Hospital Affiliated First People's Hospital, Shanghai Jiao Tong University, Shanghai, China.
authors.forename: XiaoLi
authors.initials: X
authors.lastname: Lou
authors.affiliation: Department of Central Laboratory, Songjiang Hospital Affiliated First People's Hospital, Shanghai Jiao Tong University, Shanghai, China.
authors.forename: HongWei
authors.initials: H
authors.lastname: Chen
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000235:genetics* / Q000276:immunology*; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D053222:Fas Ligand Protein / Q000378:metabolism; D008099:Liver / Q000473:pathology; D008168:Lung / Q000473:pathology; D008214:Lymphocytes / Q000276:immunology* / Q000378:metabolism*; D051379:Mice; D053323:Receptors, Tumor Necrosis Factor, Member 6b / Q000235:genetics*; D018805:Sepsis / Q000235:genetics* / Q000276:immunology* / Q000401:mortality; D013154:Spleen / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D013950:Thymus Gland / Q000276:immunology / Q000378:metabolism / Q000473:pathology
chemical_list: D016207:Cytokines; D053222:Fas Ligand Protein; D053323:Receptors, Tumor Necrosis Factor, Member 6b