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

• Published in: Multiple sclerosis Vol. 10; no. 5; pp. 494 - 498
• Main Authors: Feng, Juan, Misu, Tatsuro, Fujihara, Kazuo, Sakoda, Saburo, Nakatsuji, Yuji, Fukaura, Hikoaki, Kikuchi, Seiji, Tashiro, Kunio, Suzumura, Akio, Ishii, Naoto, Sugamura, Kazuo, Nakashima, Ichiro, Itoyama, Yasuto
• Format: Journal Article
• Language: English
• Published: Thousand Oaks, CA SAGE Publications 01.10.2004; Arnold; Sage Publications Ltd
• Subjects: Adult; Biological and medical sciences; Degenerative and inherited degenerative diseases of the nervous system. Leukodystrophies. Prion diseases; Female; Flow Cytometry; Humans; Immunomodulators; Killer Cells, Natural - cytology; Killer Cells, Natural - drug effects; Lymphocytes - cytology; Lymphocytes - drug effects; Male; Medical sciences; Multiple sclerosis and variants. Guillain barré syndrome and other inflammatory polyneuropathies. Leukoencephalitis; Multiple Sclerosis, Relapsing-Remitting - drug therapy; Multiple Sclerosis, Relapsing-Remitting - immunology; Neurology; Pharmacology. Drug treatments; Phosphodiesterase Inhibitors - administration & dosage; Pyridines - administration & dosage; Th1 Cells - cytology; Th1 Cells - drug effects; Th2 Cells - cytology; Th2 Cells - drug effects; cytokine; natural killer T cell; ibudilast; multiple sclerosis; phosphodiesterase inhibitor; therapy; Multiple sclerosis; Nervous system diseases; Cytokine; Inflammatory disease; Natural killer cell; Treatment; Central nervous system disease; T-Lymphocyte; Ibudilast; Degenerative disease
• ISSN: 1352-4585; 1477-0970
• DOI: 10.1191/1352458504ms1070oa

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.