title: Interleukin-33 upregulation in peripheral leukocytes and CNS of multiple sclerosis patients.
abstract: Multiple sclerosis (MS) is an immune-mediated demyelinating disease of the central nervous system (CNS). Here we document for the first time that the cytokine IL-33 is upregulated in both the periphery and the CNS of MS patients. Plasma IL-33 was elevated in MS patients compared to normal subjects and a three-month treatment of MS patients with interferon β-1a resulted in a significant decrease of IL-33 levels. Similarly, stimulated cultured lymphocytes and macrophages from MS patients had elevated IL-33 levels compared to normal subjects. In parallel, the transcription factor NF-κB that mediates IL-33 transcription was also elevated in leukocytes of MS patients. IL-33 was elevated in normal-appearing white matter and plaque areas from MS brains and astrocytes were identified as an important source of IL-33 expression in the CNS. In summary, IL-33 levels are elevated in the periphery and CNS of MS patients, implicating IL-33 in the pathogenesis of MS.
authors.affiliation: Department of Microbiology & Immunology, Upstate Medical University State University of New York, 750 East Adams Street, Syracuse, NY 13210, USA.
authors.forename: George P
authors.initials: GP
authors.lastname: Christophi
authors.forename: Ross C
authors.initials: RC
authors.lastname: Gruber
authors.forename: Michael
authors.initials: M
authors.lastname: Panos
authors.forename: Rebecca L
authors.initials: RL
authors.lastname: Christophi
authors.forename: Burk
authors.initials: B
authors.lastname: Jubelt
authors.forename: Paul T
authors.initials: PT
authors.lastname: Massa
mesh_terms: D000328:Adult; D002478:Cells, Cultured; D002490:Central Nervous System / Q000276:immunology*; D005260:Female; D006801:Humans; D000067596:Interleukin-33; D007378:Interleukins / Q000276:immunology*; D008214:Lymphocytes / Q000276:immunology*; D008264:Macrophages / Q000276:immunology; D008297:Male; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000276:immunology*; D016328:NF-kappa B / Q000276:immunology; D015854:Up-Regulation
chemical_list: C506536:IL33 protein, human; D000067596:Interleukin-33; D007378:Interleukins; D016328:NF-kappa B