Expression and Distribution of Tumor Necrosis Factor Alpha in Human Lumbar Intervertebral Discs: A Study in Surgical Specimen and Autopsy Controls

Abstract

STUDY DESIGN: Immunohistochemical study of tumor necrosis factor alpha expression in autopsy and surgical specimens of human lumbar intervertebral discs. OBJECTIVES: To investigate the occurrence and localization of tumor necrosis factor alpha in intervertebral disc tissue and to correlate its expression with age and the degree of disc degeneration. SUMMARY OF BACKGROUND DATA: The source and origin of discogenic pain are as yet unknown. Recently identified changes of the cellular phenotype during senescence and disc pathology with partly phagocytic properties suggest an 'inflammatory' phenotype. Tumor necrosis factor alpha is one of the most potent proinflammatory cytokines possibly modulating cellular phenotypes. It may also promote pain induction. Very little is known about the occurrence and localization of tumor necrosis factor alpha in intervertebral disc tissue of defined age and degree of histologic tissue degeneration. METHODS: The study population comprised 20 cross-sections of the complete motion segment of human lumbar vertebrae (age range 0-86 years) obtained at autopsy and 28 surgical disc specimens of individuals undergoing lumbar surgical interventions for various reasons. The temporospatial distribution of tumor necrosis factor alpha-positive cells using a polyclonal antibody was correlated with a histologic degeneration score. RESULTS: Tumor necrosis factor alpha is expressed substantially in (nonsymptomatic) autopsy material in fetal/infantile and older adult nucleus pulposus, whereas it is sparsely expressed in adolescent and young adult nucleus pulposus. In the anulus fibrosus, tumor necrosis factor alpha is not found in young adults (<25 years), but then significantly increases in extent. In contrast, symptomatic nucleus pulposus and anulus fibrosus (surgical material) contain substantially more tumor necrosis factor alpha-positive cells. A significant positive correlation of tumor necrosis factor alpha expression and disc degeneration (histologic degeneration score) was found for the anulus fibrosus in both sample groups. In the surgical material, an additional significant positive correlation was identified for nuclear tumor necrosis factor alpha, disc degeneration, and age. CONCLUSIONS: Tumor necrosis factor alpha is substantially expressed in disc material of symptomatic patients (surgical specimens) in comparison to samples taken at autopsy. The expression of tumor necrosis factor alpha in early fetal/infantile nucleus pulposus may indicate 'physiologic' tissue disarrangement with closure of the blood vessel canals. The expression of tumor necrosis factor alpha in adult discs, in contrast, is statistically associated with disc degeneration. Its occurrence in adults of more advanced age suggests that tumor necrosis factor alpha is not involved in the initiation of disc degeneration, but may be associated with further promotion of degenerative disarrangement and pain induction.