Tumor necrosis factor alpha expression in the spinal cord of human T-cell lymphotrophic virus type I associated myelopathy/tropical spastic paraparesis patients

Abstract

HTLV-I Associated Myelopathy Tropical Spastic Paraparesis (HAM/TSP) is a chronic degenerative disease mainly affecting the spinal cord. The pathogenesis of HAM/TSP is unknown, but is thought to involve immunopathogenic mechanisms. Several reports have detected inflammatory cytokines such as tumor necrosis factor alpha (TNF alpha) in HAM/TSP patients. In this study, we used in situ hybridization (ISH) to examine the expression of TNF alpha RNA in spinal cord autopsy specimens from three chronic HAM/TSP patients with long-term disease (10-20 years duration). ISH identified many TNF alpha-expressing cells throughout all three patient's spinal cord tissues. Two patient's spinal cord tissue showed inflammatory cells, however double labeling by ISH for TNF alpha RNA with immunohisto-chemistry for CD45RO (a marker for memory T-cells) or CD-68 (a marker for microglia/macrophages) did not colocalize TNF alpha RNA with either CD45RO or CD-68 positive cells. Therefore, TNF alpha is expressed in the spinal cord of chronic HAM/TSP patients compared to normal controls and TNF alpha-expressing cells do not appear to be memory T-cells, microglia or macrophages.