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Interleukin-18 in pediatric rheumatic diseases

Prencipe, Giusi; Bracaglia, Claudia; De Benedetti, Fabrizio

doi: 10.1097/BOR.0000000000000634

Purpose of review IL-18 is a pleiotropic cytokine involved in the regulation of innate and adaptive immune responses. IL-18 pro-inflammatory activities are finely regulated in vivo by the inhibitory effects of the soluble IL-18-binding protein (IL-18BP). The elevation of circulating levels of IL-18 has been described in children with systemic juvenile idiopathic arthritis (sJIA). In the recent years, the role of IL-18 in the pathogenesis of secondary haemophagocytic lymphohistiocytosis (sHLH), also referred to as macrophage activation syndrome (MAS), in the context of autoinflammatory diseases, including sJIA, is emerging.

Recent findings A large number of studies in patients and animal models pointed to the imbalance in IL-18/IL-18BP levels, causing increased systemic levels of free bioactive IL-18, as a predisposing factor in the development of MAS. Although the exact mechanisms involved in the development of MAS are not clearly understood, increasing evidence demonstrate the role of IL-18 in upregulating the production of interferon (IFN)-γ.

Summary On the basis of the first emerging data on the possibility of blocking IL-18, we here discuss the scientific rationale for neutralizing the IL-18/IFNγ axis in the prevention and treatment of sHLH and MAS.

Division of Rheumatology, IRCCS Bambino Gesù Children's Hospital, Rome, Italy

Correspondence to Fabrizio De Benedetti, MD, Piazza S.Onofrio, 4, 00165, Rome, Italy. Tel: +39 06 68592659; e-mail:

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