Time-dependent cytokine deviation toward the Th2 side in Japanese multiple sclerosis patients with interferon beta-1b

• Published in: Journal of the neurological sciences 2004-07, Vol.222 (1), p.65-73
• Main Authors: Ochi, Hirofumi, Feng-Jun, Mei, Osoegawa, Manabu, Minohara, Motozumi, Murai, Hiroyuki, Taniwaki, Takayuki, Kira, Jun-ichi
• Format: Article
• Language: English
• Subjects: Adult; Biological and medical sciences; CD4-Positive T-Lymphocytes - drug effects; CD4-Positive T-Lymphocytes - immunology; CD8-Positive T-Lymphocytes - drug effects; CD8-Positive T-Lymphocytes - immunology; Cytokines - blood; Cytokines - immunology; Cytokines - secretion; Down-Regulation - drug effects; Down-Regulation - immunology; Female; Flow Cytometry; Humans; IFNγ; IL-13; IL-4; Interferon beta; Interferon beta-1b; Interferon-beta - pharmacology; Interferon-beta - therapeutic use; Interferon-gamma - blood; Interferon-gamma - immunology; Interferon-gamma - secretion; Interleukin-13 - blood; Interleukin-13 - immunology; Interleukin-13 - secretion; Interleukin-4 - blood; Interleukin-4 - immunology; Interleukin-4 - secretion; Interleukin-5 - blood; Interleukin-5 - immunology; Interleukin-5 - secretion; Japan; Male; Medical sciences; Middle Aged; Multiple sclerosis; Multiple Sclerosis, Relapsing-Remitting - drug therapy; Multiple Sclerosis, Relapsing-Remitting - immunology; Multiple Sclerosis, Relapsing-Remitting - physiopathology; Neurology; Opticospinal MS; Recurrence; Th1; Th2; Th2 Cells - drug effects; Th2 Cells - immunology; Th2 Cells - secretion; Up-Regulation - drug effects; Up-Regulation - immunology
• ISSN: 0022-510X; 1878-5883
• DOI: 10.1016/j.jns.2004.04.012

To address the immune mechanism sustaining interferon beta (IFNβ) efficacy in multiple sclerosis (MS), we longitudinally analyzed expressions of IFN-γ, IL-4, IL-5 and IL-13 in CD4 + T cells and CD8 + T cells in 22 Japanese MS patients (16 patients with conventional MS and 6 with opticospinal MS) undergoing IFNβ using flow cytometry. During the 48-week observation period, five opticospinal MS patients (83%) relapsed compared to only four conventional MS patients (25%); the frequency of relapsed patients was significantly higher in the former ( p=0.046). The effects of IFNβ on individual cytokines were time-dependent and altered cytokine productions were particularly evident in CD4 + rather than CD8 + T cells. A decreased intracellular IFN-γ/IL-4 ratio in CD4 + T cells was thus evident soon after the initiation of therapy, and persisted for the entire 1 year follow-up period, regardless of whether or not the patient relapsed ( p