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Mult Scler. 2011 Jul;17(7):851-66. doi: 10.1177/1352458511399797. Epub 2011 May 11.

The balance of pro-inflammatory and trophic factors in multiple sclerosis patients: effects of acute relapse and immunomodulatory treatment.

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  • 1Department of Neurology, Hannover Medical School, Hannover, Germany. Lindquist.Sabine@mh-hannover.de

Abstract

BACKGROUND:

In multiple sclerosis inflammation is primarily injurious to the central nervous system, but its therapeutic suppression might inhibit repair-promoting factors.

OBJECTIVES:

We aimed at better describing the complexity of biological effects during an acute relapse and analysed the effects of intervention with high-dose i.v. glucocorticoids and immunomodulatory treatment with interferon-beta (IFNβ).

METHODS:

We studied the intracellular expression levels of the pro-inflammatory mediators tumour necrosis factor alpha (TNFα) and inducible nitric oxide synthase (iNOS) together with the neurotrophins ciliary neurotrophic factor (CNTF) and brain-derived neurotrophic factor (BDNF) in freshly isolated peripheral blood mononuclear cells of multiple sclerosis patients during an acute relapse, after intervention with i.v. methylprednisolone and at baseline, using a highly quantitative flow-cytometric approach.

RESULTS:

We demonstrated the expression of CNTF in human leucocytes. We showed that CNTF levels differed in acutely relapsing multiple sclerosis patients compared with controls and increased after corticosteroid treatment. CNTF can counteract the toxicity of TNFα towards oligodendrocytes and we found TNFα increased during acute relapses. Following corticosteroids, neither TNFα nor iNOS expression was reduced. Levels of BDNF were not affected by glucocorticoids, but increased during IFNβ therapy. However, IFNβ also increased the expression of iNOS and major histocompatibility complex class I (MHC-I), underlining its immunomodulatory potential.

CONCLUSIONS:

Multiple sclerosis patients might benefit from reparative, and not solely from anti-inflammatory, effects of glucocorticoids. Interactive effects of glucocorticoid- and IFNβ-treatment need to be considered to improve neuroprotection and remyelination resulting from immunomodulatory treatment.

PMID:
21561957
DOI:
10.1177/1352458511399797
[PubMed - indexed for MEDLINE]
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