Multiple sclerosis: pro- and anti-inflammatory cytokines and metalloproteinases are affected differentially by treatment with IFN-beta.
Interferon-beta (IFN-beta) has a beneficial influence on the course of multiple sclerosis (MS) and has become standard treatment of this disease, though its mechanisms of action are incompletely understood. This study examines the effect of IFN-beta treatment on the cytokines IL-6, TNF-alpha, IFN-gamma and IL-10; the metalloproteinases MMP-3, -7 and -9 and the tissue inhibitor of metalloproteinase-1 (TIMP-1). IFN-beta treatment resulted in decreased numbers of mononuclear cells (MNC) secreting IL-6 and TNF-alpha and expressing mRNA of MMP-3 and MMP-9 compared to pretreatment levels. On the contrary, numbers of IL-10 secreting MNC and TIMP-1 mRNA expressing were augmented during IFN-beta therapy. Whether the down-regulatory effects on pro-inflammatory and upregulatory effects on anti-inflammatory molecules are a direct result of IFN-beta on the immune system or secondary to clinical stabilization of MS pathology induced by IFN-beta remains to be evaluated.
Ozenci
V
V
Division of Neurology, Unit of Neuroimmunology, Karolinska Institutet, Huddinge University Hospital, S-141 86 Huddinge, Stockholm, Sweden. volkan.ozenci@neurotec.ki.se
Kouwenhoven
M
M
Teleshova
N
N
Pashenkov
M
M
Fredrikson
S
S
Link
H
H
D002478:Cells, Cultured; D016207:Cytokines / Q000378:metabolism*; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects*; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D006801:Humans; D017403:In Situ Hybridization; D007249:Inflammation / Q000201:enzymology / Q000235:genetics / Q000378:metabolism; D016899:Interferon-beta / Q000494:pharmacology* / Q000627:therapeutic use; D007371:Interferon-gamma / Q000378:metabolism; D007378:Interleukins / Q000378:metabolism; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000378:metabolism; D008137:Longitudinal Studies; D008297:Male; D019278:Matrix Metalloproteinase 3 / Q000235:genetics; D020783:Matrix Metalloproteinase 7 / Q000235:genetics; D020780:Matrix Metalloproteinase 9 / Q000235:genetics; D020782:Matrix Metalloproteinases / Q000235:genetics*; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000188:drug therapy / Q000201:enzymology* / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000235:genetics; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D016207:Cytokines; D007378:Interleukins; D012333:RNA, Messenger; D019715:Tissue Inhibitor of Metalloproteinase-1; D014409:Tumor Necrosis Factor-alpha; D016899:Interferon-beta; D007371:Interferon-gamma; D020782:Matrix Metalloproteinases; D019278:Matrix Metalloproteinase 3; D020783:Matrix Metalloproteinase 7; D020780:Matrix Metalloproteinase 9