INVESTIGATION OF GLUCOCORTICOID SENSITIVITY IN MULTIPLE SCLEROSIS PATIENTS IN RELAPSE
- Maria Eleftheria A. Evangelopoulos, Greece
Abstract
Background and Aims
Glucocorticoids (GCs) are used for the treatment of relapse multiple sclerosis.(MS). Decreased sensitivity to GCs in MS patients has been associated with lack of suppressive effect of GCs on inflammatory molecules, increased resistance to apoptosis which in turn affect the response to high intravenous methylprednisolone (IVMP). We investigated GC-sensitivity by measuring the effect of IVMP treatment on transactivation of anti-inflammatory, anti-apoptotic and apoptotic genes (GILZ, MCL-1 and NOXA respectively) in accordance to clinical outcome.
Methods
We studied 24 MS patients: clinically isolated syndrome (CIS/n=9), relapsing remitting (RRMS/n=8) and secondary progressive (SPMS/n=7) under relaspe. Patients underwent treatment with IVMP (1000mg/day) for 5 consecutive days. Blood was drawn on before and 1 hour after IVMP on day 1 and also 1h after 5th IVMp. GIlZ, MCL-1 and NOXA gene expression was determined by qPCR. The Expanded Disability Status was also evaluated before and after IVMP (on 5th day) and all patients were divided according to their clinical response into two groups.
Results
Our data demonstrate that the GILZ and MCL-1 gene expression were significantly higher after first IVMP injection (day1) in clinical responders compared to non-clinical responders (p≤0.05). However, the NOXA gene expression 1h after 5th IVMP was significantly higher in clinical responders as compared to non-clinical responders (p≤0.05).
Conclusions
Our findings suggest that the differential GILZ and MCL-1 gene expression between clinical responders and non-clinical responders implicate the importance of GILZ and MCL-1 as possible markers for predicting glucocorticoid sensitivity and response to GC-therapy in MS patients after the first IVMP treatment.