Similar biological effect of high-dose oral versus intravenous methylprednisolone in multiple sclerosis relapses

Abstract

Our aim was to investigate differences in immune mechanisms in multiple sclerosis (MS) relapse, after high-dose oral methylprednisolone (oMP) or intravenous methylprednisolone (ivMP). We measured serum cytokines (IL-2, IL-4, IL-6, IL-10, IL-17, TNF-α and IFN-γ) in 39 of 49 MS patients with moderate-severe relapse, whom were treated with ivMP or oMP in a placebo-controlled, non-inferiority clinical trial. We assessed these cytokine levels at baseline and at 1 and 4 weeks post-treatment. The cytokine levels between oMP and ivMP were similar at any time. Proinflammatory cytokines (IL-6 and IFN-γ) were significantly decreased in both groups at week 1 (p = 0.05 / p = 0.03) and at week 4 (p = 0.04 / p = 0.05). This study provides further confirmatory evidence that oMP is not inferior to ivMP.

Trial registration: clinicaltrials.gov identifier: NCT00753792

Keywords

Clinical trial cytokines dosage forms methylprednisolone multiple sclerosis relapses

Get full access to this article

View all access options for this article.

References

Cannella

Raine

CS.

The adhesion molecule and cytokine profile of multiple sclerosis lesions. Ann Neurol 1995; 37: 424–435.

Gayo

Mozo

Suarez

. Glucocorticoids increase IL-10 expression in multiple sclerosis patients with acute relapse. J Neuroimmunol 1998; 85: 122–130.

Pozzilli

Marinelli

Romano

. Corticosteroid treatment. J Neurol Sci 2004; 223: 47–51.

Rentzos

Nikolau

Rombos

. Effect of treatment with methylprednisolone on the serum levels of IL-12, IL-10 and CCL2 chemokine in patients with multiple sclerosis in relapse. Clin Neurol Neurosurg 2008; 110: 992–996.

Martinez-Cáceres

Barrau

Brieva

. Treatment with methylprednisolone in relapses of multiple sclerosis patients: Immunological evidence of immediate and short-term but not long-lasting effects. Clin Exp Immunol 2002; 127: 165–171.

Baraczka

Nekam

Pozsonyi

. Investigation of cytokine (tumor necrosis factor-alpha, interleukin-6, interleukin-10) concentrations in the cerebrospinal fluid of female patients with multiple sclerosis and systemic lupus erythematosus. Eur J Neurol 2004; 11: 37–42.

Matsushita

Tateishi

Isobe

. Characteristic cerebrospinal fluid cytokine/chemokine profiles in neuromyelitis optica, relapsing remitting or primary progressive multiple sclerosis. PLoS One 2013; 8: e61835.

Alam

Kyriakides

Lawden

. Methylprednisolone in multiple sclerosis: A comparison of oral with intravenous therapy at equivalent high dose. J Neurol Neurosurg Psychiatry 1993; 56: 1219–1220.

Sharrack

Hughes

Morris

. The effect of oral and intravenous methylprednisolone treatment on subsequent relapse rate in multiple sclerosis. J Neurol Sci 2000; 173: 73–77.

10.

Martinelli

Rocca

Annovazzi

. A short-term randomized MRI study of high-dose oral vs intravenous methylprednisolone in MS. Neurology 2009; 73: 1842–1848.

11.

Ramo-Tello

Grau-López

Tintoré

. A randomized clinical trial of oral versus intravenous methylprednisolone for relapse of MS. Mult Scler 2014; 20: 717–725.

12.

Kim

Park

. Corticosteroid inhibits IL-4 signaling through down-regulation of IL4 receptor and STAT6 activity. FEBS Lett 2002; 518: 53–59.

13.

Dufour

Salmaggi

La Mantia

. High-dose methylprednisolone treatment-induced changes in immunological parameters in progressive MS patients. Int J Neurosci 1994; 75: 119–128.

14.

Petermann

Khorn

Cytokines and effector T-cell subsets causing autoimmune CNS disease. FEBS Lett 2011; 585: 3747–3757.