Targeting interferon-γ in hyperinflammation: opportunities and challenges

Area of Science:

• Immunology
• Cytokine Biology
• Translational Medicine

Background:

• Interferon-gamma (IFNγ) is a key cytokine involved in immune responses.
• Overproduction of IFNγ is implicated in severe hyperinflammatory and immune-mediated diseases.
• IFNγ influences B cells and T follicular helper cells, suggesting a role in systemic lupus erythematosus.

Purpose of the Study:

• To explore the role of IFNγ in human diseases.
• To identify and study IFNγ-related biomarkers for managing hyperinflammatory conditions.
• To assess the clinical utility of biomarkers like CXCL9 in reflecting IFNγ activity.

Main Methods:

• Review of animal models and translational research in patients.
• Identification and study of IFNγ-related biomarkers (e.g., phosphorylated STAT1, neopterin, CXCL9).
• Evaluation of IFNγ-neutralizing agents in clinical trials for hyperinflammatory diseases.

Main Results:

• IFNγ plays a role in primary and secondary haemophagocytic lymphohistiocytosis, macrophage activation syndrome, and cytokine release syndrome.
• IFNγ-neutralizing agents demonstrate efficacy in treating primary haemophagocytic lymphohistiocytosis.
• Circulating CXCL9 levels are emerging as a reliable biomarker for IFNγ production in clinical practice.

Conclusions:

• IFNγ is a critical factor in various hyperinflammatory diseases.
• Biomarkers such as CXCL9 are valuable for assessing IFNγ activity and guiding treatment.
• Targeting IFNγ shows therapeutic potential for severe inflammatory conditions.