Tumour necrosis factor alpha mRNA expression in early multiple sclerosis lesions: Correlation with demyelinating activity and oligodendrocyte pathology
✍ Scribed by Andreas Bitsch; Tanja Kuhlmann; Christiane Da Costa; Stephanie Bunkowski; Thomas Polak; Wolfgang Brück
- Publisher
- John Wiley and Sons
- Year
- 2000
- Tongue
- English
- Weight
- 339 KB
- Volume
- 29
- Category
- Article
- ISSN
- 0894-1491
No coin nor oath required. For personal study only.
✦ Synopsis
The precise role of tumour necrosis factor alpha (TNF␣) 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 TNF␣ 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. Nonradioactive in situ hybridisation was carried out to detect TNF␣ mRNA expressing cells. DNA fragmentation was visualised by TdT-mediated X-dUTP nick end labeling. A significantly higher number of cells expressed TNF␣ mRNA in active demyelinating lesions than in inactive or remyelinating lesions irrespective of the extent of the inflammatory infiltrate. TNF␣ mRNA expression correlated with the appearance of DNA fragmentation in T lymphocytes and oligodendrocytes within the lesions. In the periplaque white matter, expression of TNF␣ 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 TNF␣ in demyelination in human multiple sclerosis and gives further support for TNF␣-directed therapeutic strategies.