Glucocorticoid treatment reduces T-bet and pSTAT1 expression in mononuclear cells from relapsing remitting multiple sclerosis patients.
High dose glucocorticoid (GC) treatment has been demonstrated to have a short-term beneficial effect on functional recovery in relapsing multiple sclerosis (MS) patients but the exact mechanism of action of GCs in MS is unclear. We found that high dose intravenous GCs strongly reduced T-bet and pSTAT1 expression in CD4+, CD8+, CD14+ circulating cells in RRMS patients in relapse. pSTAT1and T-bet reduction was associated with the decline of IFNgamma production by PBMCs. A significant increase of AV-positive CD4+ and CD8+ T cells was detectable after GC treatment without any variation in the percentage of annexin V-positive monocytes. By in vitro analysis, patients during relapse, either before or after GC treatment, exhibited a lower proportion of apoptotic lymphocytes than remitting patients and controls. Our study suggests that GCs can modulate T-bet and STAT1 expression and that IFNgamma signalling inhibition contributes to anti-inflammatory action of GCs in the treatment of relapses of MS patients.
Frisullo
Giovanni
G
Institute of Neurology, Department of Neurosciences, Catholic University, Largo Agostino Gemelli, 8, 00168 Rome, Italy.
Nociti
Viviana
V
Iorio
Raffaele
R
Katia Patanella
Agata
A
Bianco
Assunta
A
Caggiula
Marcella
M
Sancricca
Cristina
C
Tonali
Pietro Attilio
PA
Mirabella
Massimiliano
M
Batocchi
Anna Paola
AP
D000328:Adult; D017304:Annexin A5 / Q000378:metabolism; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D002478:Cells, Cultured; D016207:Cytokines / Q000097:blood; D015536:Down-Regulation; D005260:Female; D005938:Glucocorticoids / Q000008:administration & dosage / Q000627:therapeutic use*; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000276:immunology*; D008297:Male; D008775:Methylprednisolone / Q000008:administration & dosage / Q000627:therapeutic use; D020529:Multiple Sclerosis, Relapsing-Remitting / Q000188:drug therapy*; D010766:Phosphorylation; D050794:STAT1 Transcription Factor / Q000378:metabolism*; D050796:STAT3 Transcription Factor / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects / Q000276:immunology; D020825:T-Box Domain Proteins / Q000378:metabolism*; D000098815:T-bet Transcription Factor
D017304:Annexin A5; D016207:Cytokines; D005938:Glucocorticoids; D050794:STAT1 Transcription Factor; D050796:STAT3 Transcription Factor; D020825:T-Box Domain Proteins; D000098815:T-bet Transcription Factor; D008775:Methylprednisolone