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IFNγ in human sepsis: a scoping review.

Daniel Thomas-Rüddel1, Evangelos Giamarellos-Bourboulis2, Caroline Neumann1

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Summary

Interferon gamma (IFNγ) plays a dual role in sepsis, with both high and low levels linked to poor outcomes. Targeting IFNγ may offer personalized treatment strategies for sepsis patients.

Keywords:
HyperinflammationIFNγImmunostimulatory therapyImmunosuppressionImmunosuppressive therapySepsis

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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.