This study demonstrates that overexpression of interleukin 6 (IL-6) in the brain of transgenic mice leads to severe neurologic disease, characterized by neurodegeneration, astrocytosis, angiogenesis, and induction of acute-phase proteins. The severity of the disease correlates with the level of IL-6 expression in the brain. Transgenic mice with high levels of IL-6 expression developed symptoms such as runting, tremor, ataxia, and seizures. Neuropathological findings included neurodegeneration, astrocytosis, angiogenesis, and acute-phase protein production. These findings suggest that cytokines like IL-6 can play a direct pathogenic role in inflammatory, infectious, and neurodegenerative diseases of the central nervous system (CNS). IL-6 is a prototypic cytokine with a wide range of biological actions, including those overlapping with other cytokines such as IL-1α/β and tumor necrosis factor α. IL-6 has been found in various CNS disorders, including AIDS dementia complex, viral and bacterial meningitis, multiple sclerosis, Alzheimer's disease, and trauma. Localized production of IL-6 in the CNS may be mediated by infiltrating immune-inflammatory cells, astrocytes, and microglia. Thus, IL-6 can be produced in the CNS during the host response to infection or injury and could potentially initiate or contribute to pathology. The study used a transgenic approach to overexpress IL-6 in murine astrocytes in vivo. The IL-6 gene was targeted to astrocytes using the regulatory control of the glial fibrillary acidic protein (GFAP) gene promoter. The transgenic mice exhibited a neurologic syndrome with severity correlated to IL-6 expression levels. The study also showed that IL-6 expression was specific to the brain and not observed in peripheral organs. In situ hybridization revealed widespread distribution of IL-6 RNA expression in the brains of transgenic mice, with particularly high levels in the thalamus and cerebellum. The study also found that IL-6 production in astrocytes led to significant IL-6 bioactivity in culture supernatants. Histological examination of the brains of transgenic mice revealed significant condensation of the molecular layer of the cerebellum and neovascularization. Inflammation was not observed, although a discrete perivasculitis was present in mice with high IL-6 expression. Laser scanning confocal microscope imaging of brain sections immunolabeled with anti-MAP-2 provided evidence for significant neuronal and dendritic changes in both hippocampal and cerebellar neurons. The study also found extensive astrocytosis and angiogenesis in GFAP-IL6 mice. A dramatic increase in GFAP immunoreactivity was found, especially in the thalamus, glial limitans, Bergmann glia, and cerebellar white-matter tracts. The degree ofThis study demonstrates that overexpression of interleukin 6 (IL-6) in the brain of transgenic mice leads to severe neurologic disease, characterized by neurodegeneration, astrocytosis, angiogenesis, and induction of acute-phase proteins. The severity of the disease correlates with the level of IL-6 expression in the brain. Transgenic mice with high levels of IL-6 expression developed symptoms such as runting, tremor, ataxia, and seizures. Neuropathological findings included neurodegeneration, astrocytosis, angiogenesis, and acute-phase protein production. These findings suggest that cytokines like IL-6 can play a direct pathogenic role in inflammatory, infectious, and neurodegenerative diseases of the central nervous system (CNS). IL-6 is a prototypic cytokine with a wide range of biological actions, including those overlapping with other cytokines such as IL-1α/β and tumor necrosis factor α. IL-6 has been found in various CNS disorders, including AIDS dementia complex, viral and bacterial meningitis, multiple sclerosis, Alzheimer's disease, and trauma. Localized production of IL-6 in the CNS may be mediated by infiltrating immune-inflammatory cells, astrocytes, and microglia. Thus, IL-6 can be produced in the CNS during the host response to infection or injury and could potentially initiate or contribute to pathology. The study used a transgenic approach to overexpress IL-6 in murine astrocytes in vivo. The IL-6 gene was targeted to astrocytes using the regulatory control of the glial fibrillary acidic protein (GFAP) gene promoter. The transgenic mice exhibited a neurologic syndrome with severity correlated to IL-6 expression levels. The study also showed that IL-6 expression was specific to the brain and not observed in peripheral organs. In situ hybridization revealed widespread distribution of IL-6 RNA expression in the brains of transgenic mice, with particularly high levels in the thalamus and cerebellum. The study also found that IL-6 production in astrocytes led to significant IL-6 bioactivity in culture supernatants. Histological examination of the brains of transgenic mice revealed significant condensation of the molecular layer of the cerebellum and neovascularization. Inflammation was not observed, although a discrete perivasculitis was present in mice with high IL-6 expression. Laser scanning confocal microscope imaging of brain sections immunolabeled with anti-MAP-2 provided evidence for significant neuronal and dendritic changes in both hippocampal and cerebellar neurons. The study also found extensive astrocytosis and angiogenesis in GFAP-IL6 mice. A dramatic increase in GFAP immunoreactivity was found, especially in the thalamus, glial limitans, Bergmann glia, and cerebellar white-matter tracts. The degree of