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.