title: Is suppression of apoptosis a new therapeutic target in sepsis?
abstract: Sepsis remains as a leading cause of death in critically ill patients. Unfortunately, there have been very few successful specific therapeutic agents that can significantly reduce the attributable mortality and morbidity of sepsis. Developing novel therapeutic strategies to improve outcomes of sepsis remains an important focus of ongoing research in the field of critical care medicine. Apoptosis has recently been identified as an important mechanism of cell death and evidence suggests that prevention of cell apoptosis can improve survival in animal models of sepsis and endotoxaemia. In this review article, we summarise the critical role of apoptosis of the immune cells in the pathophysiology of sepsis and propose that blocking cell-signaling pathways leading to apoptosis may present a promising specific therapy for sepsis. Various methods to inhibit apoptosis including the cell surface Fas receptor pathway inhibitors, caspase inhibitors, over-expression of anti-apoptotic genes and small interfering ribonucleic acid therapy are discussed.
authors.affiliation: Department of Anesthesilogy, Chhatrapati Shahuji Maharaj Medical University, Lucknow, Uttar Pradesh, India. mamtaharjaidoctor@yahoo.co.in
authors.forename: M
authors.initials: M
authors.lastname: Harjai
authors.forename: J
authors.initials: J
authors.lastname: Bogra
authors.forename: M
authors.initials: M
authors.lastname: Kohli
authors.forename: A B
authors.initials: AB
authors.lastname: Pant
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D051017:Apoptosis Regulatory Proteins / Q000502:physiology; D051023:BH3 Interacting Domain Death Agonist Protein / Q000502:physiology; D000072224:Bcl-2-Like Protein 11; D045304:Cytochromes c / Q000502:physiology; D006801:Humans; D008565:Membrane Proteins / Q000502:physiology; D011518:Proto-Oncogene Proteins / Q000502:physiology; D018805:Sepsis / Q000188:drug therapy* / Q000473:pathology
chemical_list: D051017:Apoptosis Regulatory Proteins; C000606775:BCL2L11 protein, human; D051023:BH3 Interacting Domain Death Agonist Protein; D000072224:Bcl-2-Like Protein 11; D008565:Membrane Proteins; D011518:Proto-Oncogene Proteins; D045304:Cytochromes c