Interleukin-33 upregulation in peripheral leukocytes and CNS of multiple sclerosis patients

• Published in: Clinical immunology (Orlando, Fla.) Vol. 142; no. 3; pp. 308 - 319
• Main Authors: Christophi, George P., Gruber, Ross C., Panos, Michael, Christophi, Rebecca L., Jubelt, Burk, Massa, Paul T.
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier Inc 01.03.2012; Elsevier
• Subjects: Adult; Allergy and Immunology; Astrocytes; Autoimmunity; Biological and medical sciences; Cells, Cultured; Central Nervous System - immunology; Demyelination; EAE; Female; Fundamental and applied biological sciences. Psychology; Fundamental immunology; Humans; IL-33; Inflammation; Interleukin-33; Interleukins - immunology; Lymphocytes - immunology; Macrophages - immunology; Male; Medical sciences; Middle Aged; Multiple Sclerosis - immunology; Multiple sclerosis and variants. Guillain barré syndrome and other inflammatory polyneuropathies. Leukoencephalitis; Neurology; NF-kappa B - immunology; Up-Regulation; Autoimmunity; EAE; Inflammation; Demyelination; Astrocytes; IL-33; Human; Nervous system diseases; Multiple sclerosis; Leukocyte; Neuroglia; Interleukin; Cytokine; Astrocyte; Experimental allergic encephalomyelitis; Inflammatory disease; Immunology; Central nervous system disease
• ISSN: 1521-6616; 1521-7035; 1521-7035
• DOI: 10.1016/j.clim.2011.11.007

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. ► The first study documenting IL-33 expression in multiple sclerosis. ► IL-33 was elevated in plasma and activated leukocytes of MS patients. ► Three-month treatment with interferon β-1a suppressed plasma IL-33 levels. ► IL-33 was elevated in brains of MS patients and astrocytes highly expressed IL-33. ► IL-33 is elevated in the periphery and CNS, implicating IL-33 in MS pathogenesis.