title: Interleukin-17 in transverse myelitis and multiple sclerosis.
abstract: CSF IL-6 is elevated in transverse myelitis (TM) and predicts disability. Since IL-17 regulates cytokines (TNFalpha, IL-1beta and IL-6) known to stimulate IL-6 production by astrocytes, we sought to determine whether IL-17 was increased in TM and MS compared to healthy controls (HC) and other neurologic diseases (OND). IL-17 and IL-6 levels were measured in stimulated peripheral blood mononuclear cell (PBMC) supernatants from HC, MS, TM and OND. IL-17 was increased in TM compared to HC, MS, and OND (mean pg/ml+/-standard error; HC: 36.1+/-11.7, MS: 89.4+/-23.3, TM: 302.6+/-152.5, OND: 41.2+/-13.0, p=0.01). IL-6 was increased in TM relative to MS and HC (HC: 2624 pg/ml+/-641, MS: 6129+/-982, TM: 12,536+/-2657, OND: 6920+/-1801, p<0.002). MS patients with early disease (<2 years) also had increased levels of IL-17 (p<0.04) and IL-6 (p<0.05). Cytokine neutralization experiments demonstrated that IL-6 was the main inducer of astrocyte IL-6 production. We conclude that IL-17 and IL-6 production from PBMC in TM and early MS are increased and induce astrocyte IL-6 production through IL-6.
authors.affiliation: The Johns Hopkins University School of Medicine, Department of Neurology, Baltimore, MD 21287-6965, United States.
authors.forename: Jerome J
authors.initials: JJ
authors.lastname: Graber
authors.forename: S Rameeza
authors.initials: SR
authors.lastname: Allie
authors.forename: Katherine M
authors.initials: KM
authors.lastname: Mullen
authors.forename: Melina V
authors.initials: MV
authors.lastname: Jones
authors.forename: Tongguang
authors.initials: T
authors.lastname: Wang
authors.forename: Chitra
authors.initials: C
authors.lastname: Krishnan
authors.forename: Adam I
authors.initials: AI
authors.lastname: Kaplin
authors.forename: Avi
authors.initials: A
authors.lastname: Nath
authors.forename: Douglas A
authors.initials: DA
authors.lastname: Kerr
authors.forename: Peter A
authors.initials: PA
authors.lastname: Calabresi
mesh_terms: D000328:Adult; D001253:Astrocytes / Q000187:drug effects / Q000378:metabolism; D001921:Brain / Q000166:cytology; D002478:Cells, Cultured; D016207:Cytokines / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005260:Female; D005333:Fetus; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D006801:Humans; D007211:Indoles; D019410:Interleukin-16 / Q000378:metabolism; D020381:Interleukin-17 / Q000378:metabolism*; D007963:Leukocytes, Mononuclear / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D009103:Multiple Sclerosis / Q000134:cerebrospinal fluid / Q000378:metabolism* / Q000473:pathology; D009188:Myelitis, Transverse / Q000134:cerebrospinal fluid / Q000378:metabolism* / Q000473:pathology; D009422:Nervous System Diseases / Q000134:cerebrospinal fluid / Q000378:metabolism / Q000473:pathology; D013997:Time Factors
chemical_list: D016207:Cytokines; D005904:Glial Fibrillary Acidic Protein; D007211:Indoles; D019410:Interleukin-16; D020381:Interleukin-17; C007293:DAPI