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 GRα to GRβ was positively correlated with clinical score changes. However, there was no difference in the GRα/GRβ ratio between SHD and low-dose MP groups. SRp30c mRNA was correlated with GRβ expression.


CONCLUSIONS
This study indicates that the GRα/GRβ ratio is associated with GC sensitivity, and SRp30c may play an important role in promoting alternative splicing of GR pre-mRNA to generate GRβ in EAE rats. Compared with low-dose MP, SHD MP does not improve efficacy or induce GC resistance.
Wei
Zhi-sheng
ZS
Department of Neurology, First Affiliated Hospital, Guangdong Pharmaceutical University, Guangzhou, China.
Hong
Ming-fan
MF
Su
Quan-xi
QX
Wang
Xiao-hui
XH
Yu
Qing-yun
QY
Peng
Zhong-xing
ZX
Zhang
Ming-xing
MX
Jie
Ao
A
Wang
Rui
R
Huang
Ye-qing
YQ
D000818:Animals; D016207:Cytokines / Q000096:biosynthesis; D004305:Dose-Response Relationship, Drug; D004306:Dose-Response Relationship, Immunologic; D004351:Drug Resistance / Q000276:immunology*; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000188:drug therapy* / Q000276:immunology* / Q000473:pathology; D005260:Female; D006168:Guinea Pigs; D008297:Male; D008775:Methylprednisolone / Q000494:pharmacology* / Q000627:therapeutic use; D009687:Nuclear Proteins / Q000096:biosynthesis; D020033:Protein Isoforms / Q000096:biosynthesis; D016601:RNA-Binding Proteins / Q000096:biosynthesis; D051381:Rats; D017208:Rats, Wistar; D011965:Receptors, Glucocorticoid / Q000096:biosynthesis; D000068103:Serine-Arginine Splicing Factors; D016896:Treatment Outcome
D016207:Cytokines; D009687:Nuclear Proteins; D020033:Protein Isoforms; D016601:RNA-Binding Proteins; D011965:Receptors, Glucocorticoid; D000068103:Serine-Arginine Splicing Factors; D008775:Methylprednisolone