実験的アレルギー性脳脊髄炎に対するPhosphodiesterase Inhibitorの抑制効果

Abstract

The effects of combined therapy of subtypes of phosphodiesterase inhibitors (PDEIs), which can inhibit the production of TNFα, were studied in rats with actively induced experirnental allergic encephalomyelitis (EAE) by myelin basic protein. The rats with EAE were treated with a single PDEI or the combination of two or three PDEIs (amrinone: type3 PDEI,50mg/kg/day, papaverin HCl:non-specific type, 20mg/kg/day, and dipyridamole,50mg/kg/day). Each agent or the combination was injected throughout days 1-10 or days 1-21 or days 8-21(only three PDEIs). In the group treated with three PDEIs for days 1-21, the incidence of the disease was less than half and the clinical score was significantly decreased compared to the control group treated with normal saline. The other groups treated with one or two PDEIs were partially effective. On pathological examination, mononuclear cell infiltration in the spinal cord was decreased in the most effective group. The mRNA expression of TNFα by the RT-PCR method in peripheral blood cells and spinal cord was decreased in the group treated with three PDEIs. This study suggests that the combination therapy of three subtypes of PDEIs is effective in the treatment of EAE in the rat and the combination therapy of PDEIs rnay be of benefit in the treatment of multiple sclerosis.