Ibudilast, a nonselective phosphodiesterase inhibitor, regulates Th1/Th2 balance and NKT cell subset in multiple sclerosis

Juan Feng, Tatsuro Misu, Kazuo Fujihara, Saburo Sakoda, Yuji Nakatsuji, Hikoaki Fukaura, Seiji Kikuchi, Kunio Tashiro, Akio Suzumura, Naoto Ishii, Kazuo Sugamura, Ichiro Nakashima, Yasuto Itoyama

Research output: Contribution to journalArticlepeer-review

40 Citations (Scopus)

Abstract

We investigated the immunoregulatory effects of ibudilast, a nonselective phosphodiesterase inhibitor, at a clinically applicable dose (60 mg/day p.o. for four weeks) in multiple sclerosis (MS) patients. Sensitive real-time PCR for quantifying cytokine mRNA in the blood CD4 + cells revealed that the ibudilast monotherapy significantly reduced tumour necrosis factor-α and interferon (IFN)-γ mRNA and the IFN-γ/interleukin-4 mRNA ratio, suggesting a shift in the cytokine profile from Th1 toward Th2 dominancy. In a flow cytometric analysis, natural killer T cells, which have been reported to relate to Th2 responses in MS and its animal model (experimental autoimmune encephalomyelitis), increased significantly after the therapy. None of the significant immunological changes were seen in healthy subjects or untreated MS patients. lbudilast may be a promising therapy for MS and its clinical effects warrant further study.

Original languageEnglish
Pages (from-to)494-498
Number of pages5
JournalMultiple Sclerosis
Volume10
Issue number5
DOIs
Publication statusPublished - 2004 Oct 1

Keywords

  • Cytokine
  • Ibudilast
  • Multiple sclerosis
  • Natural killer T cell
  • Phosphodiesterase inhibitor
  • Therapy

ASJC Scopus subject areas

  • Neurology
  • Clinical Neurology

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