Tumour necrosis factor alpha mRNA expression in early multiple sclerosis lesions: Correlation with demyelinating activity and oligodendrocyte pathology

• Published in: Glia Vol. 29; no. 4; pp. 366 - 375
• Main Authors: Bitsch, Andreas, Kuhlmann, Tanja, Da Costa, Christiane, Bunkowski, Stephanie, Polak, Thomas, Brück, Wolfgang
• Format: Journal Article
• Language: English
• Published: New York John Wiley & Sons, Inc 15-02-2000; Wiley-Liss
• Subjects: Adolescent; Adult; Apoptosis; Biological and medical sciences; Biopsy, Needle; Demyelinating Diseases - genetics; demyelination; DNA Fragmentation; Female; Gene Expression Regulation; Humans; In Situ Hybridization; macrophages; Male; Medical sciences; microglia; Middle Aged; Multiple Sclerosis - genetics; Multiple Sclerosis - metabolism; Multiple Sclerosis - pathology; Multiple sclerosis and variants. Guillain barré syndrome and other inflammatory polyneuropathies. Leukoencephalitis; Nerve Tissue Proteins - biosynthesis; Nerve Tissue Proteins - genetics; Neurology; Oligodendroglia - pathology; RNA, Messenger - biosynthesis; RNA, Messenger - genetics; T lymphocytes; Tumor Necrosis Factor-alpha - biosynthesis; Tumor Necrosis Factor-alpha - genetics; Human; Immunopathology; Nervous system diseases; Multiple sclerosis; Neuroglia; Cytokine; Autoimmune disease; Gene expression; Inflammatory disease; Microglia; Oligodendrocyte; Demyelination; Central nervous system disease; T-Lymphocyte; Lesion; Tumor necrosis factor α; Apoptosis; Macrophage
• ISSN: 0894-1491; 1098-1136
• DOI: 10.1002/(SICI)1098-1136(20000215)29:4<366::AID-GLIA7>3.0.CO;2-Y

The precise role of tumour necrosis factor alpha (TNFα) in multiple sclerosis (MS) is still controversial. Most findings from the animal model experimental allergic encephalomyelitis have yet to be confirmed in multiple sclerosis. The aim of this study was to define the significance of TNFα with respect to the hallmark of MS, that is demyelination. Therefore, 78 lesion areas from diagnostic brain biopsies of 32 patients were analysed. Lesion demyelinating activity was classified by the presence of myelin degradation products in macrophages and macrophage activation markers. Non‐radioactive in situ hybridisation was carried out to detect TNFα mRNA expressing cells. DNA fragmentation was visualised by TdT‐mediated X‐dUTP nick end labeling. A significantly higher number of cells expressed TNFα mRNA in active demyelinating lesions than in inactive or remyelinating lesions irrespective of the extent of the inflammatory infiltrate. TNFα mRNA expression correlated with the appearance of DNA fragmentation in T lymphocytes and oligodendrocytes within the lesions. In the periplaque white matter, expression of TNFα mRNA negatively correlated with oligodendrocyte numbers. These data support previous findings from animal models and in vitro experiments. Although not proving, the current study strongly suggests a pathogenic role of TNFα in demyelination in human multiple sclerosis and gives further support for TNFα‐directed therapeutic strategies. GLIA 29:366–375, 2000. © 2000 Wiley‐Liss, Inc.