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Published on: December 9, 2022
A two-decade journey in identifying high mobility group box 1 (HMGB1) and procathepsin L (pCTS-L) as potential
Jianhua Li1, Cassie Shu Zhu1, Li He2
1The Feinstein Institutes for Medical Research, Northwell Health, Manhasset, NY, USA.
Introduction:
Microbial infections and resultant sepsis are leading causes of death in hospitals, representing approximately 20% of total deaths worldwide. Despite the difficulties in translating experimental insights into effective therapies for often heterogenous patient populations, an improved understanding of the pathogenic mechanisms underlying experimental sepsis is still urgently needed. Sepsis is partly attributable to dysregulated innate immune responses manifested by hyperinflammation and immunosuppression at different stages of microbial infections.
Areas Covered:
Here we review our recent progress in searching for late-acting mediators of experimental sepsis and propose high mobility group box 1 (HMGB1) and procathepsin-L (pCTS-L) as potential therapeutic targets for improving outcomes of lethal sepsis and other infectious diseases.
Expert Opinion:
It will be important to evaluate the efficacy of HMGB1- or pCTS-L-targeting agents for the clinical management of human sepsis and other infectious diseases in future studies.
Insights
Sepsis, a major cause of hospital deaths, involves immune dysregulation. High mobility group box 1 (HMGB1) and procathepsin-L (pCTS-L) are identified as potential therapeutic targets for sepsis treatment.
Area of Science:
- Immunology
- Infectious Diseases
- Critical Care Medicine
Background:
- Sepsis is a leading global cause of mortality, accounting for approximately 20% of all deaths worldwide.
- Pathogenic mechanisms of sepsis involve complex dysregulated innate immune responses, including hyperinflammation and immunosuppression.
- Effective sepsis therapies are challenging due to patient heterogeneity and difficulties in translating experimental findings.
Purpose of the Study:
- To review recent advancements in identifying late-acting mediators of experimental sepsis.
- To propose high mobility group box 1 (HMGB1) and procathepsin-L (pCTS-L) as novel therapeutic targets for sepsis.
Main Methods:
- Literature review of experimental sepsis research.
- Identification and analysis of potential therapeutic targets based on pathogenic mechanisms.
Main Results:
- High mobility group box 1 (HMGB1) is implicated as a late-acting mediator in experimental sepsis.
- Procathepsin-L (pCTS-L) is also identified as a potential therapeutic target for lethal sepsis.
- These mediators play a role in the dysregulated immune responses characteristic of sepsis.
Conclusions:
- HMGB1 and pCTS-L represent promising targets for developing novel sepsis therapies.
- Targeting HMGB1 or pCTS-L may improve outcomes in lethal sepsis and other infectious diseases.
- Further clinical studies are warranted to evaluate the efficacy of HMGB1- or pCTS-L-targeting agents in human sepsis.
