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Published on: June 15, 2019
Is suppression of apoptosis a new therapeutic target in sepsis?
1Department of Anesthesilogy, Chhatrapati Shahuji Maharaj Medical University, Lucknow, Uttar Pradesh, India. mamtaharjaidoctor@yahoo.co.in
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.
Insights
Sepsis is a major cause of death. Blocking immune cell apoptosis, programmed cell death, may offer a novel therapeutic strategy to improve sepsis survival rates.
Area of Science:
- Critical care medicine
- Immunology
- Molecular biology
Background:
- Sepsis is a leading cause of mortality in critically ill patients.
- Few effective therapies exist to reduce sepsis-related death and illness.
- Apoptosis (programmed cell death) is a key cell death mechanism in sepsis.
Purpose of the Study:
- To review the role of immune cell apoptosis in sepsis pathophysiology.
- To propose targeting apoptosis pathways as a potential sepsis therapy.
Main Methods:
- Review of existing literature on sepsis and apoptosis.
- Discussion of various apoptosis inhibition strategies.
Main Results:
- Immune cell apoptosis significantly contributes to sepsis progression.
- Preventing apoptosis improved survival in animal sepsis models.
Conclusions:
- Targeting cell-signaling pathways that induce apoptosis is a promising therapeutic approach for sepsis.
- Methods like Fas receptor inhibitors, caspase inhibitors, and gene-based therapies warrant further investigation.
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