title: 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 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.
authors.affiliation: Department of Neurology, First Affiliated Hospital, Guangdong Pharmaceutical University, Guangzhou, China.
authors.forename: Zhi-sheng
authors.initials: ZS
authors.lastname: Wei
authors.forename: Ming-fan
authors.initials: MF
authors.lastname: Hong
authors.forename: Quan-xi
authors.initials: QX
authors.lastname: Su
authors.forename: Xiao-hui
authors.initials: XH
authors.lastname: Wang
authors.forename: Qing-yun
authors.initials: QY
authors.lastname: Yu
authors.forename: Zhong-xing
authors.initials: ZX
authors.lastname: Peng
authors.forename: Ming-xing
authors.initials: MX
authors.lastname: Zhang
authors.forename: Ao
authors.initials: A
authors.lastname: Jie
authors.forename: Rui
authors.initials: R
authors.lastname: Wang
authors.forename: Ye-qing
authors.initials: YQ
authors.lastname: Huang
mesh_terms: 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
chemical_list: D016207:Cytokines; D009687:Nuclear Proteins; D020033:Protein Isoforms; D016601:RNA-Binding Proteins; D011965:Receptors, Glucocorticoid; D000068103:Serine-Arginine Splicing Factors; D008775:Methylprednisolone