Super-high-dose methylprednisolone does not improve efficacy or induce glucocorticoid resistance in experimental allergic encephalomyelitis.

ABSTRACT

OBJECTIVE: To investigate whether a super-high dose (SHD) of methylprednisolone (MP) improves its efficacy or induces glucocorticoid (GC) resistance, and to explore the potential mechanisms of GC resistance in experimental allergic encephalomyelitis (EAE). METHODS: The therapeutic effects of SHD and low-dose MP were evaluated in EAE by analyzing clinical scores, pathological changes and cytokine production. Immunohistochemistry and RT-PCR were used to investigate the expression of GC receptor (GR) isoforms and splicing factor SRp30c. RESULTS: Both MP doses had similar therapeutic effects. The ratio of GRα to GRß was positively correlated with clinical score changes. However, there was no difference in the GRα/GRß ratio between SHD and low-dose MP groups. SRp30c mRNA was correlated with GRß expression. CONCLUSION: This study indicates that the GRα/GRß ratio is associated with GC sensitivity, and SRp30c may play an important role in promoting alternative splicing of GR pre-mRNA to generate GRß in EAE rats. Compared with low-dose MP, SHD MP does not improve efficacy or induce GC resistance.