Interleukin-18 in pediatric rheumatic diseases
Giusi Prencipe1, Claudia Bracaglia, Fabrizio De Benedetti
1Division of Rheumatology, IRCCS Bambino Gesù Children's Hospital, Rome, Italy.
Current Opinion in Rheumatology
|June 14, 2019
Summary
Interleukin-18 (IL-18) imbalance contributes to macrophage activation syndrome (MAS) in systemic juvenile idiopathic arthritis. Neutralizing the IL-18/interferon-gamma (IFNγ) pathway may prevent and treat MAS.
Area of Science:
- Immunology
- Cytokine biology
- Autoinflammatory diseases
Background:
- Interleukin-18 (IL-18) is a key cytokine regulating immune responses.
- Its activity is controlled by IL-18-binding protein (IL-18BP).
- Elevated IL-18 levels are observed in systemic juvenile idiopathic arthritis (sJIA).
Purpose of the Study:
- To review the role of IL-18 in the pathogenesis of secondary hemophagocytic lymphohistiocytosis (sHLH)/macrophage activation syndrome (MAS).
- To discuss the potential of targeting the IL-18/IFNγ axis for sHLH/MAS treatment.
Main Methods:
- Literature review focusing on IL-18, IL-18BP, sJIA, sHLH, and MAS.
- Analysis of existing data on IL-18/IL-18BP imbalance and its link to MAS.
- Evaluation of the therapeutic potential of IL-18 neutralization.
Main Results:
- Imbalance in IL-18/IL-18BP levels promotes MAS development.
- Increased free IL-18 contributes to MAS pathogenesis.
- IL-18 upregulates interferon-gamma (IFNγ) production, a key mediator in MAS.
Conclusions:
- The IL-18/IFNγ axis is a critical factor in MAS pathogenesis.
- Neutralizing IL-18 offers a potential therapeutic strategy for sHLH and MAS.
- Targeting this pathway may be beneficial in autoinflammatory diseases like sJIA.
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