Ibudilast, a nonselective phosphodiesterase inhibitor, regulates Th1/Th2 balance and NKT cell subset in multiple sclerosis.
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.
Department of Neurology, Tohoku University School of Medicine, 1-1 Seiryomachi, Aoba-ku, Sendai 980-8574, Japan.
Juan
J
Feng
Tatsuro
T
Misu
Kazuo
K
Fujihara
Saburo
S
Sakoda
Yuji
Y
Nakatsuji
Hikoaki
H
Fukaura
Seiji
S
Kikuchi
Kunio
K
Tashiro
Akio
A
Suzumura
Naoto
N
Ishii
Kazuo
K
Sugamura
Ichiro
I
Nakashima
Yasuto
Y
Itoyama
D000328:Adult; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D007694:Killer Cells, Natural / Q000166:cytology / Q000187:drug effects; D008214:Lymphocytes / Q000166:cytology / Q000187:drug effects*; D008297:Male; D020529:Multiple Sclerosis, Relapsing-Remitting / Q000188:drug therapy* / Q000276:immunology*; D010726:Phosphodiesterase Inhibitors / Q000008:administration & dosage*; D011725:Pyridines / Q000008:administration & dosage*; D018417:Th1 Cells / Q000166:cytology / Q000187:drug effects; D018418:Th2 Cells / Q000166:cytology / Q000187:drug effects; D007212:Indolizines; D011720:Pyrazoles
D010726:Phosphodiesterase Inhibitors; D011725:Pyridines; C038366:ibudilast; D007212:Indolizines; D011720:Pyrazoles