Additive effect of prostaglandin E2 and adenosine in mouse experimental autoimmune encephalomyelitis

Experimental autoimmune encephalomyelitis (EAE) is an animal model of multiple sclerosis (MS), which is a T cell-mediated autoimmune disease of the central nervous system (CNS). Emerging evidence indicates that both prostaglandin E-2 (PGE(2)) and adenosine play important roles in immune inflammation although the mechanism remains unclear. In the study, we examined individual and combined effect of PGE(2) and adenosine during EAE development. The results showed that both PGE(2) and adenosine could inhibit EAE progression and they in combination showed substantially higher inhibition than each modality used alone. On the other hand, using specific agonists or antagonists for PGE(2) and adenosine receptors indicated that the suppression of EAE development was mainly mediated by EP4 and A(2A) receptors. Furthermore, combined PGE(2) and adenosine treatment significantly suppressed the production of IFN-gamma and IL-17 via EP4 and A(2A) receptors. Taken together, PGE(2) and adenosine in combination could protect EAE mouse from serious EAE through limiting the over-reactive effects of T cells via EP4 and A(2A) receptors. Crown Copyright (C) 2013 Published by Elsevier Inc. All rights reserved.