Analysis of Tissue Distribution of TNF-α, TNF-α-Receptors, and the Activating TNF-α–Converting Enzyme Suggests Activation of the TNF-α System in the Aging Intervertebral Disc

We immunohistochemically analyzed the expression and localization of TNF-a, its receptors TNF-RI and -RII, and the TNF-α-activating enzyme TACE in human autopsy (n = 63) and surgical (n = 35) lumbar intervertebral disc samples. In parallel, the TNF-α-mRNA was quantified by reverse transcriptase-polymerase chain reaction (RT-PCR). All samples were morphometrically evaluated for the proportion of positively labeled cells in the different anatomical regions of the disc. We detected a significant and comparable expression of all four parameters beginning in young adult age (c. 18 years) and being most extensive in the nucleus pulposus. This level was slightly reduced in older age discs. The annulus fibrosus contained significantly less labeled cells. In accord, the number of TNF-α-transcripts was elevated in most cases with immunohistochemical TNF-α expression. We provide clear evidence that TNF-a is expressed in discs of increasing age, which correlates with histomorphological signs of disc degeneration. In consequence, TNF-α seems to be activated (by the converting enzyme TACE) and biologically active through its receptors in human lumbar disc tissue.