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

Juan Feng1, Tatsuro Misu, Kazuo Fujihara

  • 1Department of Neurology, Tohoku University School of Medicine, 1-1 Seiryomachi, Aoba-ku, Sendai 980-8574, Japan.

Multiple Sclerosis (Houndmills, Basingstoke, England)
|October 9, 2004
PubMed

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-alpha and interferon (IFN)-gamma mRNA and the IFN-gamma/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. Ibudilast may be a promising therapy for MS and its clinical effects warrant further study.

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