IL-6 and TNFalpha expression in brains of twitcher, quaking and normal mice

Cytokines have been postulated to play a pathogenic role in twitcher mice, which are an animal model of globoid cell leukodystrophy. In particular, TNFalpha promotes oligodendrocyte and myelin pathology, and IL-6 expression is induced in astrocyte and microglial cultures that have been incubated with TNFalpha or myelin debris, respectively. It is unknown whether these cytokines are expressed in twitcher mice. The objectives of the present study were to develop an immunohistochemical method to detect TNFalpha and IL-6 in the mouse CNS, and then utilize this method to identify the cell types expressing these cytokines, and their spatial distribution, in the brains of normal, twitcher and quaking mice. In normal mice, IL-6 was found in ependymal cells, Bergmann glia, in processes that were adjacent or attached to the ventricles or pial surface, and in lightly stained processes in white matter. These processes were identified to belong to astrocytes and microglia. IL-6 staining was dramatically increased in twitcher mice. Astrocytes, with reactive features, and microglia were labeled in the cerebral cortex, basal ganglia, subcortical white matter, pons, medulla and cerebellar white matter. IL-6-positive reactive astrocytes were less abundant in quaking mice than twitcher mice. Cells expressing TNFalpha were rare or absent in normal and quaking mice. In twitcher mice, TNFalpha-positive macrophages were present at a lower concentration in cerebral white matter than in the pons and medulla, which have more advanced demyelination. These data demonstrate that pathological events induce the expressions of TNFalpha and IL-6 in the CNS of twitcher mice.