title: Insights into sepsis therapeutic design based on the apoptotic death pathway.
abstract: Sepsis remains the leading cause of death in critically ill patients. A major problem contributing to sepsis-related high mortality is the lack of effective medical treatment. Thus, the key goal in critical care medicine is to develop novel therapeutic strategies that will impact favorably on septic patient outcome. While it is generally accepted that sepsis is an inflammatory state resulting from the systemic response to infection, apoptosis is implicated to be an important mechanism of the death of lymphocytes, gastrointestinal and lung epithelial cells, and vascular endothelial cells associated with the development of multiple organ failure in sepsis. The pivotal role of cell apoptosis is now highlighted by multiple studies demonstrating that prevention of cell apoptosis can improve survival in clinically relevant animal models of sepsis. In this review article, we address the scientific rationale for remedying apoptotic cell death in sepsis and propose that therapeutic efforts aimed at blocking cell signaling pathways leading to apoptosis may represent an attractive target for sepsis therapy.
authors.affiliation: Department of Molecular and Medical Pharmacology, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, 2630 Sugitani, Toyama 930-0194, Japan. yhattori@med.u-toyama.ac.jp
authors.forename: Yuichi
authors.initials: Y
authors.lastname: Hattori
authors.forename: Ken-ichi
authors.initials: K
authors.lastname: Takano
authors.forename: Hiroki
authors.initials: H
authors.lastname: Teramae
authors.forename: Seiji
authors.initials: S
authors.lastname: Yamamoto
authors.forename: Hiroki
authors.initials: H
authors.lastname: Yokoo
authors.forename: Naoyuki
authors.initials: N
authors.lastname: Matsuda
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology*; D061945:Caspase Inhibitors; D020169:Caspases / Q000235:genetics / Q000502:physiology; D042783:Endothelial Cells / Q000473:pathology; D004791:Enzyme Inhibitors / Q000494:pharmacology / Q000627:therapeutic use; D004847:Epithelial Cells / Q000473:pathology; D020868:Gene Silencing; D005938:Glucocorticoids / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology; D006801:Humans; D008214:Lymphocytes / Q000473:pathology; D058990:Molecular Targeted Therapy; D034741:RNA, Small Interfering / Q000627:therapeutic use; D018805:Sepsis / Q000209:etiology* / Q000628:therapy*; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology*
chemical_list: D061945:Caspase Inhibitors; D004791:Enzyme Inhibitors; D005938:Glucocorticoids; D034741:RNA, Small Interfering; D020169:Caspases