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

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

Tatsuro Misu

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

Kazuo Fujihara

Department of Neurology, Tohoku University School of Medicine, 1-1 Seiryomachi, Aoba-ku, Sendai 980-8574, Japan, fujikazu{at}em.neurol.med.tohoku.ac.jp

Saburo Sakoda

Department of Neurology, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita, Osaka 565-0871, Japan

Yuji Nakatsuji

Department of Neurology, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita, Osaka 565-0871, Japan

Hikoaki Fukaura

Department of Neurology, Hokkaido University School of Medicine, North 15, West 7, Kita-ku, Sapporo 060-8638, Japan

Seiji Kikuchi

Department of Neurology, Hokkaido University School of Medicine, North 15, West 7, Kita-ku, Sapporo 060-8638, Japan

Kunio Tashiro

Department of Neurology, Hokkaido University School of Medicine, North 15, West 7, Kita-ku, Sapporo 060-8638, Japan

Akio Suzumura

Department of Neuroimmunology, Research Institute of Environmental Medicine, Nagoya University, Furomachi, Chikusa-ku, Nagoya 464-8601, Japan

Naoto Ishii

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

Kazuo Sugamura

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

Ichiro Nakashima

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

Yasuto Itoyama

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

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-a and interferon (IFN)-g mRNA and the IFN-g/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.

Key Words: cytokine • ibudilast • multiple sclerosis • natural killer T cell • phosphodiesterase inhibitor • therapy

Multiple Sclerosis, Vol. 10, No. 5, 494-498 (2004)
DOI: 10.1191/1352458504ms1070oa


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