Glucocorticoids increase IL-10 expression in multiple sclerosis patients with acute relapse

Area of Science:

• Immunology
• Neuroscience
• Pharmacology

Background:

• High-dose glucocorticoids (GCs) are a standard treatment for acute relapsing-remitting multiple sclerosis (MS) attacks.
• GCs modulate the cytokine network, contributing to their therapeutic effects.
• The specific impact of GCs on the immunosuppressive cytokine IL-10 in MS requires further elucidation.

Purpose of the Study:

• To investigate the effect of methylprednisolone (MP), a GC, on IL-10 production in MS patients during relapse.
• To examine the in vitro effects of MP on IL-10 expression in peripheral blood mononuclear cells (PBMCs).
• To determine the impact of MP on both spontaneous and lipopolysaccharide (LPS)-induced IL-10 production.

Main Methods:

• Blood samples from MS patients before and after MP treatment were analyzed for IL-10, TNF-alpha, and IFN-gamma mRNA and protein levels.
• In vitro studies used normal PBMCs treated with MP to assess IL-10 mRNA and protein expression.
• RT-PCR, ELISA, and flow cytometry were employed for quantification; the glucocorticoid receptor antagonist RU486 was used to confirm steroid specificity.

Main Results:

• Seven of nine MS patients showed increased IL-10 mRNA and serum protein levels after MP treatment.
• MP treatment led to decreased mRNA expression of inflammatory cytokines TNF-alpha and IFN-gamma.
• In vitro, MP upregulated spontaneous IL-10 production in PBMCs, peaking at 48 hours, but downregulated LPS-induced IL-10 synthesis.

Conclusions:

• Methylprednisolone (MP) upregulates the immunosuppressive cytokine IL-10 in multiple sclerosis patients and in vitro.
• GCs may exert anti-inflammatory effects in MS by increasing IL-10 production and decreasing pro-inflammatory cytokines.
• MP exhibits differential effects on spontaneous versus induced IL-10 production, highlighting a complex regulatory mechanism.