[Molecular mechanisms underlying the pathogenesis of septic multiple organ failure].

Abstract

Sepsis is defined as the body's overwhelming and life-threatening response to infection that can lead to tissue damage, organ failure, and death. Since bacterial infection is one of the main causes of sepsis, appropriate antimicrobial therapy remains the cornerstone of sepsis and septic shock management. However, since sepsis is a multifaceted chaos involving inflammation and anti-inflammation disbalance leading to the unregulated widespread release of inflammatory mediators, cytokines, and pathogen-related molecules leading to system-wide organ dysfunction, the whole body control to prevent the progression of organ dysfunction is needed. In sepsis and septic shock, pathogen-associated molecular patterns (PAMPs), such as bacterial exotoxins, cause direct cellular damage and/or trigger an immune response in the host. PAMPs are recognized by pattern recognizing receptors (PRRs) expressed on immune-reactive cells. PRRs are also activated by host nuclear, mitochondrial, and cytosolic proteins, known as damage-associated molecular patterns (DAMPs) that are released from cells during sepsis. Thus, most PRRs respond to PAMPs or DAMPs by triggering activation of transcriptional factors, NF-κB, AP1, and STAT-3. On the other hand, sepsis leads to immune (lymphocytes and macrophages) and nonimmune (endothelial and epithelial cells) cell death. Apoptosis has been the major focus of research on cell death in sepsis, but autophagy, necrosis, necroptosis, pyroptosis, NETosis, and ferroptosis may also play an important role in this critical situation. The recent development in our understanding regarding the cellular pathogenesis of sepsis will help in developing new treatment of sepsis.

• Authors: Naoyuki Matsuda, Takuji Machida, Yuichi Hattori
• Journal: Nihon yakurigaku zasshi. Folia pharmacologica Japonica (Nihon Yakurigaku Zasshi) Vol. 159 Issue 2 Pg. 101-106 ( 2024) ISSN: 0015-5691 [Print] Japan
• PMID: 38432917 (Publication Type: English Abstract, Journal Article)

Chemical References

• Pathogen-Associated Molecular Pattern Molecules
• Alarmins

Topics

• Humans
• Multiple Organ Failure (etiology)
• Shock, Septic
• Pathogen-Associated Molecular Pattern Molecules
• Sepsis
• Apoptosis
• Alarmins