Ibudilast, a phosphodiesterase inhibitor, ameliorates experimental autoimmune encephalomyelitis in Dark August rats.
A phosphodiesterase inhibitor (PDEI), Ibudilast, which has been in wide use for the management of bronchial asthma and cerebrovascular disease in Japan, was tested for its clinical efficacy on experimental autoimmune encephalomyelitis (EAE) in Dark August rats. The severity of acute EAE was significantly ameliorated by prophylactic oral treatment with Ibudilast (10 mg/kg per day) starting on the day of immunization, although it did not modify the course of the disease when it was given after the onset of the first clinical sign of EAE. Histologically, inflammatory cell infiltration in the lumbar spinal cord was significantly reduced in Ibudilast-treated animals as compared to control animals. Ibudilast mildly suppressed MBP-induced proliferation of T cells in regional lymph nodes, the secretion of interferon-gamma from T cells activated by MBP in CFA, and the secretion of tumor necrosis factor-alpha from macrophages. While the in vitro studies did not suggest difference between Ibudilast and other PDEIs such as rolipram, the clinical dose of Ibudilast is approximately 200-fold higher than that of rolipram and the effective dose of Ibudilast was relatively close to what has been therapeutically used in patients. Thus, Ibudilast may be a candidate for clinical use for patients with multiple sclerosis. 1999 Elsevier Science B.V. All rights reserved.
Fujimoto
T
T
Department of Neurology, Osaka University Medical School, Suita, Japan.
Sakoda
S
S
Fujimura
H
H
Yanagihara
T
T
D000284:Administration, Oral; D000818:Animals; D002455:Cell Division / Q000187:drug effects / Q000276:immunology; D004195:Disease Models, Animal; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000188:drug therapy* / Q000276:immunology; D005260:Female; D007371:Interferon-gamma / Q000096:biosynthesis / Q000276:immunology; D008070:Lipopolysaccharides / Q000494:pharmacology; D009103:Multiple Sclerosis / Q000188:drug therapy / Q000276:immunology; D009569:Nitric Oxide / Q000096:biosynthesis; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology*; D011725:Pyridines / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D013116:Spinal Cord / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D016176:T-Lymphocyte Subsets / Q000166:cytology / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis / Q000276:immunology; D007212:Indolizines; D011720:Pyrazoles
D007371:Interferon-gamma; D008070:Lipopolysaccharides; D009569:Nitric Oxide; D010726:Phosphodiesterase Inhibitors; D011725:Pyridines; D014409:Tumor Necrosis Factor-alpha; C038366:ibudilast; D007212:Indolizines; D011720:Pyrazoles