EAE is an inflammatory autoimmune process of the CNS that resembles multiple sclerosis (MS) and provides a useful animal model for the evaluation of mechanisms of action for potential immunomodulatory therapies.  Oral ACTH can decrease clinical disease, IL-17 and Th1-like encephalitogenic IFN-g secretion and increase T_reg frequency. The mechanism by which oral ACTH decreases inflammatory proteins and increases T_reg cell frequencies is unknown. 

B6 mice were immunized with MOG peptide 35-55 and gavaged with scrambled ACTH (s-MSH) peptide or ACTH 1-39 during ongoing disease. 

Ingested (oral) ACTH inhibited ongoing clinical disease. In the lamina propria (LP) immune compartment, there were significantly less CD11b+ IL-6 and IL-17 producing lymphocytes from ACTH fed mice compared to s-MSH fed mice. There was also a decrease in the frequency of IL-17 and IFN-g producing spleen cells and an increase in CD4+FoxP3+T_reg cell frequency in ACTH fed mice compared to s-MSH fed control spleens.  There were less IFN-g producing CNS lymphocytes in ACTH fed mice compared to s-MSH fed control CNS.

Ingested ACTH inhibits EAE clinical disease by inhibiting IL-6 in the GALT.