Interleukin-1beta, -6, -12 and tumor necrosis factor-alpha expression in brains of dogs with canine distemper virus infection.
Canine distemper virus infection in dogs is commonly associated with demyelinating central nervous system lesions. Investigations on viral protein expression by studying mRNA and protein distribution together with the characterization of CD4 and CD8 inflammatory cells and MHC class II up-regulation revealed a biphasic disease process. To further investigate the cellular interactions in the different plaque types the cerebella of 14 dogs with confirmed distemper infection were investigated for expression of interleukin (IL)-1beta, -6, -12 and tumor necrosis factor-alpha (TNF) by immunohistochemistry using rabbit polyclonal anti-cytokine antibodies. T-cells and astrocytes were identified with rabbit anti CD3- and GFAP-monoclonal and polyclonal antibodies, respectively; and microglia/macrophages were characterized by their ability to bind lectin from Bandeiraea simplicifolia (BS-1). To further name the cytokine expressing cells immunoenzymatic double staining using DAB and New Fuchsin was performed. White matter lesions were classified according to histopathological criteria into acute, subacute and chronic. Canine distemper virus nucleoprotein antigen was demonstrated in nearly all plaques, except in older plaques where virus was not present within the plaque but adjacent to the lesion. IL-1 expression was observed to varying degrees in all types of lesions. Most often IL-1 was present in CD3 and BS-1 positive cells in the brain parenchyma in earlier plaques and comprising perivascular cuffs found in chronic plaques. IL-6 expression was present in all lesions, and followed a similar distribution pattern as IL-1. IL-12 displayed very often a granular extracellular pattern of immunoreactivity, especially in the brain parenchyma, and was found only in individual perivascular cells. TNF staining, predominantly found in astrocytes, was present in lesions of various types; however, staining appeared to be stronger in acute lesions and decreased in chronic plaques. In the latter, TNF seemed to be more prominent in areas adjacent to the plaques. Summarizing, in early non-demyelinating lesions without overt inflammation TNF seemed to be important, whereas in distemper lesions with inflammatory infiltrates IL-1 and to a lesser degree IL-6 were more prominent. These results imply that TNF may be involved in the pathogenesis of early demyelination in nervous distemper.
Gröne
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A
Institut für Veterinär-Pathologie, Justus-Liebig-Universität Giessen, Giessen, Germany.
Alldinger
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S
Baumgärtner
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W
D000818:Animals; D001253:Astrocytes / Q000821:virology; D001921:Brain / Q000276:immunology* / Q000473:pathology / Q000821:virology*; D016207:Cytokines / Q000032:analysis / Q000096:biosynthesis* / Q000276:immunology; D004216:Distemper / Q000276:immunology* / Q000473:pathology; D004217:Distemper Virus, Canine; D004283:Dog Diseases / Q000276:immunology* / Q000473:pathology / Q000821:virology*; D004285:Dogs; D007375:Interleukin-1 / Q000032:analysis / Q000096:biosynthesis / Q000276:immunology; D018664:Interleukin-12 / Q000032:analysis / Q000096:biosynthesis / Q000276:immunology; D015850:Interleukin-6 / Q000032:analysis / Q000096:biosynthesis / Q000276:immunology; D008264:Macrophages / Q000276:immunology / Q000821:virology; D017628:Microglia / Q000821:virology; D013601:T-Lymphocytes / Q000276:immunology / Q000821:virology; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis / Q000096:biosynthesis / Q000276:immunology; D014764:Viral Proteins / Q000032:analysis
D016207:Cytokines; D007375:Interleukin-1; D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha; D014764:Viral Proteins; D018664:Interleukin-12