THE IMMUNOPATHOGENESIS OF POLYMICROBIAL SEPSIS.

Area of Science:

• Immunology
• Infectious Diseases
• Critical Care Medicine

Background:

• The complement system, a crucial part of innate immunity, plays a significant role in host defense.
• Dysregulation of complement activation is implicated in the pathogenesis of sepsis and other inflammatory conditions.
• Understanding complement's role in sepsis has evolved significantly over the past 25 years.

Purpose of the Study:

• To review recent advances in understanding complement activation pathways and products.
• To explore the role of complement, particularly C5a and its receptors, in sepsis and COVID-19-related lung dysfunction.
• To highlight therapeutic strategies targeting the complement system for sepsis and COVID-19.

Main Methods:

• Literature review of studies published from the late 1990s to October 2022.
• Analysis of research on complement activation pathways, anaphylatoxins (C5a), and their receptors (C5aR1, C5aR2).
• Examination of data from human and murine sepsis models, and patients with COVID-19-induced lung dysfunction.

Main Results:

• Significant progress has been made in elucidating complement activation pathways and products, including C5a.
• Complement activation contributes to both pro-inflammatory responses causing organ dysfunction and immunosuppression in sepsis.
• Research in sepsis and COVID-19 highlights the therapeutic potential of targeting the complement system.

Conclusions:

• The complement system is a key player in the pathophysiology of sepsis and COVID-19-related lung injury.
• Targeting complement activation pathways offers promising therapeutic avenues for critical illnesses.
• The field is rapidly advancing, indicating a new era in complement-based therapies.