Abstract
A Japanese randomized controlled study showed that Interferon â (IFN-â1b) therapy is clinically effective in decreasing the frequency of attacks in multiple sclerosis (MS), even in optico-spinal MS (OSMS). However, recent studies have shown that IFN-â (IFN-â1a/IFN-â1b) treatment was not effective in neuromyelitis optica (NMO) patients and that the diminished benefit of IFN-â treatment in NMO may be due to different immune responses to IFN-â. We determined longitudinally the expression of CCR5, CXCR3 and CCR4 on CD4+ T and CD8+ T cells in the blood from patients with NMO and MS treated with IFN-â1b. During a 12-month period of IFN-â1b therapy, the annualized relapse rate decreased in MS patients but not in NMO patients. There was no significant difference in the expression of the chemokine receptors between NMO and MS at baseline. The percentages of CD4+CCR5+ and CD4+CXCR3+ T cells, representative of the Th1 response, were decreased in both NMO and MS after treatment. The percentage of CD4+CCR4+ T cells, representative of the Th2 response, was decreased in MS, but those for NMO was significantly increased compared with the pretreatment levels. Our results indicate that IFN-â1b-induced up-modulation of the Th2 response in NMO patients may be the source of differences in the therapeutic response to IFN-â1b therapy. In the present study, Th2 predominance is involved in the pathogenesis of NMO.
Highlights
Interferon â (IFN-â) has been used for years in the treatment of relapsing-remitting multiple sclerosis (RRMS) with proven clinical efficacy
The percentage of CD4+ or CD8+ T cells expressing the Th1- and Th2-specific chemokine receptors among CD3+ T cells was determined by three-color flow cytometry using anti-CD3 antibody and anti-CD4 antibody or anti-CD8 antibody and one of the following anti-chemokine receptor antibodies: anti-CXCR3 antibody, anti-CCR5 antibody, and anti-CCR4 antibody
Th2 predominance may be involved in the pathogenesis of neuromyelitis optica (NMO)
Summary
Interferon â (IFN-â) has been used for years in the treatment of relapsing-remitting multiple sclerosis (RRMS) with proven clinical efficacy. Previous data has shown divergent evidence regarding the effect of IFN-â on the Th1-Th2 balance in patients with MS treated with IFN-â [1]. Most studies indicate a suppression of the generation of Th1 cytokines following treatment with IFN-â. Various T cell subsets produce IL-10 under receptor stimulation, IL-10 acts as an anti-inflammatory or Th2 cytokine. Elevated levels of IL-10 in the mononuclear cell fraction and in the serum and cerebrospinal fluid (CSF) of patients with MS treated with IFN-â have been reported. Other reports indicate a more general suppression of both Th1 and Th2 subsets in patients treated with IFN-â [2,3]. The literature remains contradictory regarding the effect of IFN-â on the Th1-Th2 balance, IFN-â might inhibit Th1 cytokines and stimulate Th2 cytokines [4,5]
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