The effect of Am-80, one of retinoids derivatives on experimental allergic encephalomyelitis in rats

Abstract

Experimental allergic encephalomyelitis (EAE) is an autoimmune model with inflammation and demyelination in the central nervous system, which resembles the human demyelinating disorder, multiple sclerosis (MS). In this study, we investigated the effect of Am-80, a synthetic retinoid, on EAE in DA rats. DA rats immunized with complete Freund's adjuvant (CFA) supplemented with myelin basic protein (MBP) developed severe EAE which reached the peak 12 to 14 days after immunization. Am-80 and prednisolone administered orally for 12 days after immunization diminished the clinical symptoms and infiltration of inflammatory cells in a dose dependent manner. However, after stopping administration, EAE recurred in DA rats treated with Am-80, but not with prednisolone. The different responses between Am-80 and prednisolone were not due to the difference in the tolerability to the MBP because both inhibited the delayed-type hypersensitivity response to MBP only during administration. To investigate the mechanism how Am-80 alone delayed the response, the expressional levels of mRNA for interleukin-6 (IL-6), interferon-gamma (IFN-γ) and tumor necrosis factor-alpha (TNF-α) in spinal cord were examined. Transcriptional levels of IL-6, IFN-γ and TNF-α were parallel with the clinical symptoms of the disease in Am-80-treated rats, that is, expressional levels of their mRNA were diminished during the administration of Am-80, which then increased as soon as the administration was stopped. Among them, the expression of IL-6 mRNA was more rapidly and highly relapsed than that of the other two cytokines mRNA. However, prednisolone attenuated transcriptions of all these cytokines throughout the experiment. Therefore, these findings suggested that the inhibition of EAE is, in part, related to the inhibition of IL-6 production. However, there are many possible mechanism in the suppression of EAE by Am-80, further experiments will be necessary.