IFNγ in human sepsis: a scoping review

Area of Science:

• Immunology
• Infectious Diseases
• Critical Care Medicine

Background:

• Interferon gamma (IFNγ) is a key cytokine orchestrating immune responses.
• IFNγ influences both immune and parenchymal cells, impacting infection and organ dysfunction.
• Recent research highlights IFNγ's critical role in sepsis pathogenesis.

Purpose of the Study:

• To review the IFNγ response during infection.
• To correlate IFNγ levels with sepsis endophenotypes in humans.
• To explore potential theranostic applications of IFNγ modulation.

Main Methods:

• Literature review of IFNγ's role in infection and sepsis.
• Analysis of associations between IFNγ levels and sepsis outcomes.
• Examination of downstream mediators like CXCL9 and their correlation with sepsis phenotypes.

Main Results:

• Both high (hyper-inflammatory) and low (immunosuppressive) IFNγ levels are associated with adverse sepsis outcomes.
• High IFNγ can induce chemokines (CXCL9, CXCL10, CXCL11), attracting lymphocytes.
• CXCL9 induction correlates with the hyper-inflammatory sepsis phenotype in a subset of patients.
• IFNγ gene polymorphisms may underlie different sepsis phenotypes.
• Pilot studies suggest potential benefits of recombinant IFNγ in counteracting immunosuppression.

Conclusions:

• IFNγ activity states are strongly associated with sepsis outcomes.
• IFNγ is a promising candidate for personalized theranostic interventions in sepsis.
• Combining IFNγ assessment with biomarkers like CXCL9 may enhance personalized medicine approaches for infection and sepsis.