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Effect of high-dose methylprednisolone treatment on CCR5 expression on blood cells in MS exacerbation
I Elovaara1, H Kuusisto, R Paalavuo
1Neuroimmunology Unit, Medical School, University of Tampere, Tampere, Finland.
Objectives:
Therapy of acute exacerbations of multiple sclerosis (MS) with high-dose intravenous methylprednisolone (IVMP) has shortened the recovery period after relapses, but the mechanisms responsible for the beneficial effects of IVMP in attacks have not been clearly established. Our purpose was to analyze the effect of IVMP on the expression of chemokine receptor 5 (CCR5) protein in blood in acute MS exacerbation.
Materials And Methods:
Blood samples were collected from 10 patients with an acute MS exacerbation and the levels of CCR5 on CD4(+) and CD8(+) T cells and CD14(+) monocytes were analyzed by using flow cytometry before IVMP, 24 h, 1 and 3 weeks after commencement of treatment.
Results:
During the 3-week period the percentages of CCR5-expressing CD4(+) T cells and CD8(+) T cells tended to decrease (P = 0.09 and 0.05, respectively), but the effect did not reach statistical significance. No marked changes were found in the percentage of CCR5-expressing CD14(+) cells.
Conclusions:
A tendency to a reduction of CCR5-expressing CD4(+) and CD8(+) blood cells induced by IVMP suggests inhibition of their potential to transmigrate into the central nervous system, which is consistent with the short-term beneficial effect of IVMP in acute exacerbation of MS.
Insights
High-dose intravenous methylprednisolone (IVMP) therapy for multiple sclerosis (MS) exacerbations may reduce T-cell migration into the central nervous system. This study observed a trend towards decreased chemokine receptor 5 (CCR5) expression on T cells after IVMP treatment.
Area of Science:
- Neuroimmunology
- Clinical Therapeutics
Background:
- Acute exacerbations of multiple sclerosis (MS) are often treated with high-dose intravenous methylprednisolone (IVMP).
- The precise mechanisms underlying IVMP's therapeutic benefits in MS relapses remain incompletely understood.
- Chemokine receptor 5 (CCR5) is implicated in T-cell trafficking to the central nervous system (CNS).
Purpose of the Study:
- To investigate the impact of IVMP on CCR5 protein expression in blood during acute MS exacerbations.
- To explore the potential role of CCR5 modulation in the efficacy of IVMP therapy for MS.
Main Methods:
- Flow cytometry was used to analyze CCR5 expression on CD4(+) T cells, CD8(+) T cells, and CD14(+) monocytes.
- Blood samples were collected from 10 MS patients during acute exacerbations.
- Analysis was performed before and at 24 hours, 1 week, and 3 weeks after initiating IVMP treatment.
Main Results:
- A non-significant trend towards decreased percentages of CCR5-expressing CD4(+) and CD8(+) T cells was observed during the 3-week treatment period (P=0.09 and P=0.05, respectively).
- No significant alterations in CCR5 expression were detected on CD14(+) monocytes.
- These findings suggest a potential inhibitory effect of IVMP on T-cell transmigration.
Conclusions:
- The observed trend of reduced CCR5 expression on T cells following IVMP treatment supports its role in limiting immune cell infiltration into the CNS.
- This modulation of CCR5 may contribute to the short-term clinical benefits of IVMP in managing acute MS relapses.
- Further research is warranted to fully elucidate the immunomodulatory effects of IVMP in MS.
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