Cytokine expression in the spinal cord lesions in HTLV-I-associated myelopathy.

Immunocytochemical staining of spinal cords from five autopsied patients with HTLV-I-associated myelopathy/tropical spastic paraparesis was performed using a panel of monoclonal or polyclonal antibodies reactive with interleukin-1 beta (IL-1 beta), interleukin-6 (IL-6), tumor necrosis factor (TNF)-alpha, interferon (IFN)-alpha, IFN-beta, IFN-gamma and transforming growth factor (TGF)-beta. In the spinal cords of patients with a shorter duration of illness, IL-1 beta, TNF-alpha, and IFN-gamma were expressed on perivascular infiltrating macrophages, astrocytes and microglia in active-chronic inflammatory lesions. In striking contrast, we rarely noted cytokine expression except for IFN-gamma in inactive-chronic lesions of patients with longer durations. In situ expression of these cytokines on microglia and astrocytes, in addition to infiltrating mononuclear cells, suggests that glial cells participate in the inflammatory process, especially in active lesions. In addition, the cytokine expression was gradually downregulated along with duration of illness.

Immunocytochemical analysis of the cellular infiltrate in the spinal cord lesions in HTLV-I-associated myelopathy.

Immunocytochemical staining of spinal cords from five autopsied patients with HAM/TSP was performed using a panel of monoclonal antibodies reactive with T cells. T cell subsets, B cells, macrophages, natural killer cells, IL-2 receptor-positive cells, and HLA-ABC and HLA-DR. In the spinal cords of patients with a shorter duration of illness, CD4+ cells, CD8+ cells and macrophages were evenly distributed in active-chronic inflammatory lesions. In striking contrast, we noted the predominance of CD8+ cells over CD4+ cells in the inactive-chronic inflammatory lesions of patients with longer duration of illness. Natural killer cells, IL-2 receptor-positive cells and B cells were only rarely present in both the active-chronic and inactive-chronic lesions. HLA-ABC was positive in endothelial cells and infiltrating mononuclear cells, and HLA-DR was positive in endothelial cells, microglia and infiltrating mononuclear cells. This study suggests that immune responses in the spinal cord lesions of HAM patients gradually change along with the duration of illness.

Experimental germanium dioxide-induced neuropathy in rats.

We report an experimental model of germanium dioxide (GeO2)-induced neuropathy in rats. More than 6 months administration of GeO2 to young rats produced neuropathy characterized by segmental demyelination/remyelination and nerve edema. Electron microscopic studies demonstrated that changes in Schwann cells, such as an increased cytoplasmic volume or disintegration of the cytoplasm, were the earliest pathological findings. Schwann cell mitochondria contained high electron-dense materials. Subsequent removal of necrotic Schwann cell debris and myelin by invading macrophages was evident. These findings suggested that the Schwann cells themselves are the primary target of the toxin. The deposition of electron-dense granules in the intra-axonal vesicles, which was suggestive of glycogen granules in mitochondria, was observed in the advanced stage of the neuropathy. The findings of endoneurial edema with splitting of myelin lamellae were noted at the early stage of demyelination. Nerve edema may be the result of GeO2-induced endothelial cell injury.