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

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.

• Authors: Sabine Lindquist, Sarah Hassinger, Jonathan A Lindquist, Michael Sailer
• Journal: Multiple sclerosis (Houndmills, Basingstoke, England) (Mult Scler) Vol. 17 Issue 7 Pg. 851-66 (Jul 2011) ISSN: 1477-0970 [Electronic] England
• PMID: 21561957 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Brain-Derived Neurotrophic Factor
• Ciliary Neurotrophic Factor
• Glucocorticoids
• Immunologic Factors
• Inflammation Mediators
• Nerve Growth Factors
• Tumor Necrosis Factor-alpha
• Interferon beta-1b
• Interferon-beta
• NOS2 protein, human
• Nitric Oxide Synthase Type II
• Methylprednisolone
• Interferon beta-1a

Topics

• Adult
• Brain-Derived Neurotrophic Factor (blood)
• Case-Control Studies
• Cell Separation (methods)
• Cells, Cultured
• Ciliary Neurotrophic Factor (blood)
• Drug Therapy, Combination
• Female
• Flow Cytometry
• Glucocorticoids (administration & dosage)
• Humans
• Immunologic Factors (therapeutic use)
• Inflammation Mediators (blood)
• Interferon beta-1a
• Interferon beta-1b
• Interferon-beta (therapeutic use)
• Leukocytes, Mononuclear (drug effects, immunology, metabolism)
• Male
• Methylprednisolone (administration & dosage)
• Middle Aged
• Multiple Sclerosis, Chronic Progressive (blood, diagnosis, drug therapy, immunology)
• Multiple Sclerosis, Relapsing-Remitting (blood, diagnosis, drug therapy, immunology)
• Nerve Growth Factors (blood)
• Nitric Oxide Synthase Type II (blood)
• Treatment Outcome
• Tumor Necrosis Factor-alpha (blood)
• Young Adult