The Neuroimmune Axis in Sepsis: From Pathophysiological Circuits to Precision Neuromodulation

Area of Science:

• Neuroimmunology
• Sepsis Pathophysiology
• Host Defense Mechanisms

Background:

• Sepsis mortality remains high due to limitations in therapies targeting immune homeostasis.
• The host response in sepsis dynamically progresses from hyperinflammation to immunosuppression.
• The nervous system's role in orchestrating host defense is increasingly recognized.

Purpose of the Study:

• To advocate for a paradigm shift in sepsis management.
• To highlight the neuroimmune axis as a central orchestrator of host defense.
• To critically evaluate emerging neuromodulation strategies for sepsis.

Main Methods:

• Review of existing literature on the neuroimmune axis in sepsis.
• Evaluation of peripheral and central nervous system pathways involved in host defense.
• Assessment of emerging neuromodulation techniques and their evidence base.

Main Results:

• The neuroimmune axis comprises peripheral pathways, central hubs, and molecular translators.
• Maladaptive plasticity in neuroimmune circuits leads to immune dysregulation in sepsis.
• Emerging neuromodulation strategies show promise but require further validation.

Conclusions:

• A neuroimmune framework offers a roadmap for proactive sepsis management.
• Precision neuromodulation, including closed-loop systems, represents a future direction.
• Further research, biomarker validation, and clinical trials are crucial for translation.