Abstract
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-γ from T cells activated by MBP
in CFA, and the secretion of tumor necrosis factor-α 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 ∼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.
Keywords
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Article info
Publication history
Accepted:
November 16,
1998
Received in revised form:
November 16,
1998
Received:
August 26,
1998
Identification
Copyright
© 1999 Elsevier Science B.V. Published by Elsevier Inc. All rights reserved.
