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Background <p>The cytokine IFNγ is released primarily by lymphocytes to initiate and orchestrate immune responses in a broad range of target cells. Whereas immune cells release inflammatory mediators and initiate antimicrobial responses when stimulated by IFNγ, parenchymal cells frequently display increased immunogenicity and incidental cell death. In addition to these well-characterized effects of IFNγ, recent studies disclose a key role of the cytokine in sepsis and organ dysfunction.</p> Main <p>This review summarizes current knowledge on the IFNγ response to infection and attempts to relate the IFNγ response to endophenotypes of sepsis in the human host. Both, excessive pro-inflammatory responses with high IFNγ and downstream mediators, such as chemokines (CXCL9), as well as immunosuppression with low IFNγ levels are associated with unfavorable outcomes in sepsis. Pilot studies suggested beneficial effects of recombinant IFNγ in counteracting immunosuppression associated with low IFNγ levels. On the other hand, IFNγ may induce macrophages to release chemokines CXCL9, 10, and 11 to attract B and T lymphocytes to the sites of infection. Downstream induction of CXCL9 (but not of CXCL10 and 11) occurring in a subset of patients with high IFNγ levels has been shown to correlate with the hyper-inflammatory phenotype of sepsis. Both, high- and low-expressing IFNγ phenotypes of sepsis, might be related to nucleotide polymorphisms of the human IFNγ gene.</p> Conclusion <p>Association of IFNγ activity states with sepsis outcome renders this key regulatory protein of immunity a top candidate for theranostic interventions in a “personalized medicine approach” to infection and sepsis, especially when combined with additional biomarkers, such as CXCL9, reflecting or even mediating maladaptive downstream actions.</p> Graphical Abstract <p></p>

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IFNγ in human sepsis: a scoping review

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年8月5日

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  • Daniel Thomas-Rüddel,
  • Evangelos Giamarellos-Bourboulis,
  • Caroline Neumann,
  • Josef Briegel,
  • Antoine Roquilly,
  • Djillali Annane,
  • Reinhard Wetzker,
  • Michael Bauer,
  • Sara Aly Abdelghany,
  • Maha Khalaf AlyAly,
  • Mohamed Gamal Elansary,
  • Shereen Mustafa Elgengeehy,
  • Heba Mostafa Elwi,
  • Yasser Sadek Nassar,
  • Rania Yehia Hash,
  • Rania Bouneb,
  • Zaineb Chelly-Dagdia,
  • Katy Diallo,
  • Jérome Fleuriet,
  • Henri-Jean Garchon,
  • Stanislas Grassin Delyle,
  • Rahma Hellali,
  • Nicholas Heming,
  • Nicolas Hunzinger,
  • Elodie Lamy,
  • Jihene Mahmoud,
  • Virginie Maxime,
  • Pierre Moine,
  • Camille Roquencourt,
  • Marie Alice Vovy,
  • Karine Zeitouni,
  • Manuela Adling-Ehrhardt,
  • Frank Bloos,
  • Sandra Frank,
  • Katharina Habler,
  • Ludwig Hinske,
  • Rainer König,
  • Dorothea Lange,
  • Margit Leitner,
  • Marcus Oswald,
  • Christina Scharf-Janssen,
  • ichael Vogeser,
  • Carlos Flores,
  • Jesús Villar

摘要

Background

The cytokine IFNγ is released primarily by lymphocytes to initiate and orchestrate immune responses in a broad range of target cells. Whereas immune cells release inflammatory mediators and initiate antimicrobial responses when stimulated by IFNγ, parenchymal cells frequently display increased immunogenicity and incidental cell death. In addition to these well-characterized effects of IFNγ, recent studies disclose a key role of the cytokine in sepsis and organ dysfunction.

Main

This review summarizes current knowledge on the IFNγ response to infection and attempts to relate the IFNγ response to endophenotypes of sepsis in the human host. Both, excessive pro-inflammatory responses with high IFNγ and downstream mediators, such as chemokines (CXCL9), as well as immunosuppression with low IFNγ levels are associated with unfavorable outcomes in sepsis. Pilot studies suggested beneficial effects of recombinant IFNγ in counteracting immunosuppression associated with low IFNγ levels. On the other hand, IFNγ may induce macrophages to release chemokines CXCL9, 10, and 11 to attract B and T lymphocytes to the sites of infection. Downstream induction of CXCL9 (but not of CXCL10 and 11) occurring in a subset of patients with high IFNγ levels has been shown to correlate with the hyper-inflammatory phenotype of sepsis. Both, high- and low-expressing IFNγ phenotypes of sepsis, might be related to nucleotide polymorphisms of the human IFNγ gene.

Conclusion

Association of IFNγ activity states with sepsis outcome renders this key regulatory protein of immunity a top candidate for theranostic interventions in a “personalized medicine approach” to infection and sepsis, especially when combined with additional biomarkers, such as CXCL9, reflecting or even mediating maladaptive downstream actions.

Graphical Abstract