IL-18: a key player in neuroinflammation and neurodegeneration?

• Published in: Trends in neurosciences (Regular ed.) 2005-09, Vol.28 (9), p.487-493
• Main Authors: Felderhoff-Mueser, Ursula, Schmidt, Oliver I., Oberholzer, Andreas, Bührer, Christoph, Stahel, Philip F.
• Format: Article
• Language: English
• Subjects: Animals; Biological and medical sciences; Brain; Brain - metabolism; Cytokines; Degenerative and inherited degenerative diseases of the nervous system. Leukodystrophies. Prion diseases; Fundamental and applied biological sciences. Psychology; General aspects. Models. Methods; Humans; Immunology; Inflammation - metabolism; Interleukin-18 - metabolism; Medical sciences; Models, Neurological; Nerve Degeneration - metabolism; Neurological disorders; Neurology; Vertebrates: nervous system and sense organs
• ISSN: 0166-2236; 1878-108X
• DOI: 10.1016/j.tins.2005.06.008

Interleukin (IL)-18 is a potent inflammatory cytokine of the IL-1 family. It is synthesized as an inactive precursor (pro-IL-18), which is cleaved into its functionally active form by caspase-1. Resident cells of the CNS express IL-18 and caspase-1 constitutively, thus providing a local IL-18-dependent immune response. Recent studies have highlighted a crucial role for IL-18 in mediating neuroinflammation and neurodegeneration in the CNS under pathological conditions, such as bacterial and viral infection, autoimmune demyelinating disease, and hypoxic–ischemic, hyperoxic and traumatic brain injuries. This review provides a synopsis of the current knowledge of IL-18-dependent mechanisms of action during acute neurodegeneration in immature and adult brains.