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

Authors: Wei, ZS  Hong, MF  Su, QX  Wang, XH  Yu, QY  Peng, ZX  Zhang, MX  Jie, A  Wang, R  Huang, YQ 
Citation: Wei ZS, etal., Neuroimmunomodulation. 2011;18(1):28-36. doi: 10.1159/000314736. Epub 2010 Jul 8.
Pubmed: (View Article at PubMed) PMID:20616573
DOI: Full-text: DOI:10.1159/000314736

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

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CRRD Object Information
CRRD ID: 11040805
Created: 2016-03-15
Species: All species
Last Modified: 2016-03-15
Status: ACTIVE



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RGD is funded by grant HL64541 from the National Heart, Lung, and Blood Institute on behalf of the NIH.