PEDIATRIC AND HERITABLE DISORDERS: Edited by Polly J. FergusonInterleukin-18 in pediatric rheumatic diseasesPrencipe, Giusi; Bracaglia, Claudia; De Benedetti, Fabrizio Author Information 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: [email protected] Current Opinion in Rheumatology: September 2019 - Volume 31 - Issue 5 - p 421-427 doi: 10.1097/BOR.0000000000000634 Buy Metrics Abstract 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. Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.