Human nucleus pulposis can respond to a pro-inflammatory stimulus

Study Design. Disc tissue obtained from patients undergoing surgery for scoliosis, lumbar radiculopathy, and discogenic pain was cultured under basal and lipopolysaccharide-stimulated conditions and the medium analyzed for production of a range of pro-inflammatory mediators. Objectives. This study was conducted to confirm that the human intervertebral disc is capable of responding to a pro-inflammatory stimulus and to identify the principal mediators involved in any response. Summary of Background Data. Degenerate human disc tissue has been shown to spontaneously secrete a number of pro-inflammatory mediators. The importance of these molecules in the pathophysiology of symptomatic disc degeneration is increasingly recognized. Human nucleus pulposus has been shown to synthesize increased amounts of interleukin (IL)-6, prostaglandin E-2 (PGE(2)), and nitric oxide in response to stimulation with IL-1beta. Murine nucleus pulposus synthesizes increased amounts of IL-1beta, IL-6, IL-10, and granulocyte-macrophage colony-stimulating factor in response to lipopolysaccharide stimulation. Lipopolysaccharide is a potent inducer of tumor necrosis factor-alpha (TNF-alpha), which is thought to play an important role in the pathophysiology of sciatica. To date, human nucleus pulposus has not been shown to secrete TNF-alpha in response to a pro-inflammatory stimulus. Methods. Human disc tissue obtained from patients undergoing surgery for scoliosis, lumbar radiculopathy, and discogenic pain was cultured under basal and lipopolysaccharide-stimulated conditions and the medium subsequently analyzed for a range of pro-inflammatory mediators. Results. None of the specimens produced any TNF-alpha, IL-1beta, granulocyte-macrophage colony-stimulating factor, or leukotriene B4. Measurable quantities of IL-6, IL-8, PGE(2), MCP-1, basic fibroblast growth factor, and transforming growth factor-beta1 were produced by a number of specimens. Lipopolysaccharide significantly increased IL-6, IL-8, and PGE(2) production in both control and degenerate disc tissue. Degenerate disc specimens responded more vigorously to lipopolysaccharide stimulation than scoliotic specimens. Conclusions. We conclude that both scoliotic and degenerate human nucleus pulposus can respond to an exogenous pro-inflammatory stimulus by secreting increased amounts of IL-6, IL-8, and PGE(2) but not TNF-alpha and that degenerate disc tissue is more sensitive to a pro-inflammatory stimulus than its scoliotic counterpart.