Super-High-Dose Methylprednisolone Does Not Improve Efficacy or Induce Glucocorticoid Resistance in Experimental Allergic Encephalomyelitis

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 GR alpha to GR beta was positively correlated with clinical score changes. However, there was no difference in the GR alpha/GR beta ratio between SHD and low-dose MP groups. SRp30c mRNA was correlated with GR beta expression. Conclusion: This study indicates that the GR alpha/GR beta ratio is associated with GC sensitivity, and SRp30c may play an important role in promoting alternative splicing of GR pre-mRNA to generate GR beta in EAE rats. Compared with low-dose MP, SHD MP does not improve efficacy or induce GC resistance. Copyright (C) 2010 S. Karger AG, Basel