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Published on: December 9, 2022
PAMPs and DAMPs in Sepsis: A Review of Their Molecular Features and Potential Clinical Implications
Sara Cicchinelli1, Giulia Pignataro2, Stefania Gemma2
1Department of Emergency, S.S. Filippo e Nicola Hospital, 67051 Avezzano, Italy.
Abstract:
Sepsis is a serious organ dysfunction caused by a dysregulated immune host reaction to a pathogen. The innate immunity is programmed to react immediately to conserved molecules, released by the pathogens (PAMPs), and the host (DAMPs). We aimed to review the molecular mechanisms of the early phases of sepsis, focusing on PAMPs, DAMPs, and their related pathways, to identify potential biomarkers. We included studies published in English and searched on PubMed® and Cochrane®. After a detailed discussion on the actual knowledge of PAMPs/DAMPs, we analyzed their role in the different organs affected by sepsis, trying to elucidate the molecular basis of some of the most-used prognostic scores for sepsis. Furthermore, we described a chronological trend for the release of PAMPs/DAMPs that may be useful to identify different subsets of septic patients, who may benefit from targeted therapies. These findings are preliminary since these pathways seem to be strongly influenced by the peculiar characteristics of different pathogens and host features. Due to these reasons, while initial findings are promising, additional studies are necessary to clarify the potential involvement of these molecular patterns in the natural evolution of sepsis and to facilitate their transition into the clinical setting.
Insights
This review explores pathogen- and danger-associated molecular patterns (PAMPs/DAMPs) in early sepsis. Understanding these molecular triggers could lead to new biomarkers and targeted therapies for sepsis patients.
Area of Science:
- Immunology
- Molecular Biology
- Critical Care Medicine
Background:
- Sepsis is a life-threatening organ dysfunction driven by a dysregulated immune response to infection.
- Innate immunity rapidly detects conserved microbial molecules (PAMPs) and host-derived danger signals (DAMPs).
Purpose of the Study:
- To review the molecular mechanisms of early sepsis, focusing on PAMPs, DAMPs, and associated pathways.
- To identify potential biomarkers for sepsis diagnosis and prognosis.
- To elucidate the molecular basis of sepsis prognostic scores.
Main Methods:
- Systematic literature review of English-language studies.
- Searches conducted on PubMed and Cochrane databases.
- Analysis of PAMPs/DAMPs roles in sepsis-affected organs and prognostic scores.
Main Results:
- Detailed discussion of current knowledge regarding PAMPs and DAMPs in sepsis.
- Analysis of PAMPs/DAMPs involvement in organ dysfunction during sepsis.
- Identification of chronological release patterns for PAMPs/DAMPs.
Conclusions:
- PAMPs/DAMPs pathways offer promising avenues for sepsis biomarker discovery and targeted therapies.
- Findings are preliminary; pathogen and host factors significantly influence these pathways.
- Further research is essential to translate these molecular insights into clinical practice for sepsis management.
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