Background: Multiple sclerosis (MS) is a chronic inflammatory and immune-mediated disease,
whose current therapeutic means are mostly effective in the relapsing-remitting form of MS, where inflammation
is still prominent, but fall short of preventing long term impairment. However, apart from inflammationmediated
demyelination, autoimmune mechanisms play a major role in MS pathophysiology, constituting a
promising pharmacological target. Phosphodiesterase (PDE) inhibitors have been approved for clinical use in
psoriasis and have undergone trials suggesting their neuroprotective effects, rendering them eligible as an option
for accessory MS therapy.
Objective: In this review, we discuss the potential role of PDE inhibitors as a complementary MS therapy.
Methods: We conducted a literature search through which we screened and comparatively assessed papers on
the effects of PDE inhibitor use, both in vitro and in animal models of MS, taking into account a number of inclusion
and exclusion criteria.
Results: In vitro studies indicated that PDE inhibitors promote remyelination and axonal sustenance, while curbing
inflammatory cell infiltration, hindering oligodendrocyte and neuronal loss and suppressing cytokine production.
In vivo studies underlined that these agents alleviate symptoms and reduce disease scores in MS animal
Conclusion: PDE inhibitors proved to be effective in addressing various aspects of MS pathogenesis both in
vitro and in vivo models. Given the latest clinical trials proving that the PDE4 inhibitor Ibudilast exerts neuroprotective
effects in patients with progressive MS, research on this field should be intensified and selective
PDE4 inhibitors with enhanced safety features should be seriously considered as prospective complementary