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.
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.
Authors: Adriana A de Jesus; Yangfeng Hou; Stephen Brooks; Louise Malle; Angelique Biancotto; Yan Huang; Katherine R Calvo; Bernadette Marrero; Susan Moir; Andrew J Oler; Zuoming Deng; Gina A Montealegre Sanchez; Amina Ahmed; Eric Allenspach; Bita Arabshahi; Edward Behrens; Susanne Benseler; Liliana Bezrodnik; Sharon Bout-Tabaku; AnneMarie C Brescia; Diane Brown; Jon M Burnham; Maria Soledad Caldirola; Ruy Carrasco; Alice Y Chan; Rolando Cimaz; Paul Dancey; Jason Dare; Marietta DeGuzman; Victoria Dimitriades; Ian Ferguson; Polly Ferguson; Laura Finn; Marco Gattorno; Alexei A Grom; Eric P Hanson; Philip J Hashkes; Christian M Hedrich; Ronit Herzog; Gerd Horneff; Rita Jerath; Elizabeth Kessler; Hanna Kim; Daniel J Kingsbury; Ronald M Laxer; Pui Y Lee; Min Ae Lee-Kirsch; Laura Lewandowski; Suzanne Li; Vibke Lilleby; Vafa Mammadova; Lakshmi N Moorthy; Gulnara Nasrullayeva; Kathleen M O'Neil; Karen Onel; Seza Ozen; Nancy Pan; Pascal Pillet; Daniela Gp Piotto; Marilynn G Punaro; Andreas Reiff; Adam Reinhardt; Lisa G Rider; Rafael Rivas-Chacon; Tova Ronis; Angela Rösen-Wolff; Johannes Roth; Natasha Mckerran Ruth; Marite Rygg; Heinrike Schmeling; Grant Schulert; Christiaan Scott; Gisella Seminario; Andrew Shulman; Vidya Sivaraman; Mary Beth Son; Yuriy Stepanovskiy; Elizabeth Stringer; Sara Taber; Maria Teresa Terreri; Cynthia Tifft; Troy Torgerson; Laura Tosi; Annet Van Royen-Kerkhof; Theresa Wampler Muskardin; Scott W Canna; Raphaela Goldbach-Mansky Journal: J Clin Invest Date: 2020-04-01 Impact factor: 14.808