title: Multiple sclerosis is associated with an imbalance between tumour necrosis factor-alpha (TNF-alpha)- and IL-10-secreting blood cells that is corrected by interferon-beta (IFN-beta) treatment.
abstract: The up-regulated B cell responses detectable in cerebrospinal fluid (CSF) and the augmented myelin antigen-specific T cell responses observed in the CSF as well as systematically in patients with multiple sclerosis (MS) suggest the involvement of cytokines in disease development and perpetuation. Here we report on the parallel involvement of TNF-alpha, IL-6, IFN-gamma and IL-10 in MS and controls, using enzyme-linked immunospot (ELISPOT) assays to detect and enumerate cytokine-secreting mononuclear cells (MNC) prepared from blood and, for IL-6 and IL-10, from CSF without in vitro stimulation. MS is associated with elevated levels of TNF-alpha-secreting blood MNC when compared with levels in groups of control patients with myasthenia gravis (MG) and other neurological diseases (OND) or healthy subjects. This elevation was confined to patients with untreated MS and not present in those examined during ongoing treatment with IFN-beta. Untreated patients with MS had lower numbers of IL-10-secreting blood MNC compared with the three control groups. In patients undergoing treatment with IFN-beta, numbers of IL-10-secreting cells were in the same range as in controls. Normalization of TNF-alpha from elevated, and of IL-10 from decreased levels could be one reason for the beneficial effects of IFN-beta in MS, although it remains to be shown whether these changes reflect phenomena primarily involved in MS pathogenesis or secondary changes. In CSF, levels of IL-10-secreting cells were higher than in blood in both MS and OND, with no difference between these groups. Systemic aberrations of IL-6 and IFN-gamma and of IL-6 in CSF in MS versus controls were only minor, irrespective of treatment with IFN-beta.
authors.affiliation: Karolinska Institutet, Division of Neurology, Unit of Neuroimmunology, Huddinge University Hospital, Stockholm, Sweden. Volkan.Ozenci@neurotec.ki.se
authors.forename: V
authors.initials: V
authors.lastname: Ozenci
authors.forename: M
authors.initials: M
authors.lastname: Kouwenhoven
authors.forename: Y M
authors.initials: YM
authors.lastname: Huang
authors.forename: P
authors.initials: P
authors.lastname: Kivisäkk
authors.forename: H
authors.initials: H
authors.lastname: Link
mesh_terms: D000328:Adult; D000368:Aged; D005260:Female; D006801:Humans; D016899:Interferon-beta / Q000627:therapeutic use*; D007371:Interferon-gamma / Q000097:blood / Q000134:cerebrospinal fluid / Q000378:metabolism; D016753:Interleukin-10 / Q000097:blood / Q000134:cerebrospinal fluid / Q000378:metabolism*; D015850:Interleukin-6 / Q000097:blood / Q000134:cerebrospinal fluid / Q000378:metabolism; D007963:Leukocytes, Mononuclear / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000097:blood / Q000134:cerebrospinal fluid / Q000188:drug therapy* / Q000473:pathology; D014409:Tumor Necrosis Factor-alpha / Q000134:cerebrospinal fluid / Q000378:metabolism*
chemical_list: D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D016899:Interferon-beta; D007371:Interferon-gamma