To investigate the effect of PDE-3 inhibitor cilostazol that inhibits cyclic AMP degradation and PDE-5 inhibitor sildenafil that inhibits cyclic GMP degradation on experimental autoimmune neuritis (EAN).

Phoshodiesterase (PDE) is implicated in cell homeostasis and the neuroinflammatory processs through hydrolysis of second messenger molecules cyclic AMP (cAMP) or cyclic GMP (cGMP) that suppresses inflammation. PDE consists of various subtypes; each of them react with their specific substrates (i.e., cAMP or cGMP) that plays unique crucial roles in various processes. However, inhibiton of the subtypes of PDE during immune-mediated neuroinflammatory diseases and their experimental animal models remains unclear.

Most rats developed weakness on their tail tips around at 10 days post immunization (DPI). The maximum weakness was observed from 14 through 18 DPI although temporal courses were different in two experiments. CLZ-treated EAN rats developed significantly mild maximum weakness, contrary, SIL-treated EAN rats exhibited accelerated recovery from weakness after spontaneous amelioration.

Histological examination showed suppression of demyelination in both PDE-I treatment. Real-time PCR analysis revealed that the recovery was coincided with Th1 to Th2 deviation.

PDE-5 inhibition may influence re-myelination or regeneration, on the other hand PDE-3 inhibition may mainly suppress inflammation or demyelination in this animal model.