Immunosuppression in Sepsis: Biomarkers and Specialized Pro-Resolving Mediators

Area of Science:

• Immunology
• Critical Care Medicine
• Pathophysiology

Background:

• Sepsis triggers a complex immune response, initially hyper-inflammatory, leading to organ damage.
• A later stage of sepsis involves paradoxical immunosuppression, increasing susceptibility to secondary infections.
• Current sepsis treatment challenges include differentiating immune stages and lack of therapies resolving inflammation without causing immunosuppression.

Purpose of the Study:

• To review the primary mechanisms driving sepsis-induced immunosuppression.
• To identify key biomarkers indicative of the immunosuppressive phase of sepsis.
• To explore the potential of specialized pro-resolving mediators (SPMs) as anti-inflammatory and non-immunosuppressive agents.

Main Methods:

• Literature review of PubMed database.
• Keywords used: sepsis, lymphocyte apoptosis, macrophage exhaustion, myeloid-derived suppressor cells (MDSCs), biomarkers, and SPMs.
• Focused on three main immunosuppression mechanisms: lymphocyte apoptosis, monocyte/macrophage exhaustion, and MDSC migration.

Main Results:

• Key immunosuppression mechanisms include lymphocyte apoptosis, macrophage exhaustion, and increased MDSC migration.
• Biomarkers for septic immunosuppression include elevated MDSCs and IL-10, decreased lymphocytes and HLA-DR, and increased GPR18.
• Specialized pro-resolving mediators (SPMs) show promise in resolving inflammation without immunosuppression in preclinical models.

Conclusions:

• Understanding sepsis-induced immunosuppression mechanisms and biomarkers is crucial for effective treatment.
• Myeloid-derived suppressor cells (MDSCs) and associated biomarkers play a significant role in septic immunosuppression.
• Specialized pro-resolving mediators (SPMs) represent a potential therapeutic avenue for sepsis, offering anti-inflammatory effects without immunosuppression.