Human nucleus pulposis can respond to a pro-inflammatory stimulus

Abstract

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 E2 (PGE2), 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, PGE2, MCP-1, basic fibroblast growth factor, and trans forming growth factor-beta1 were produced by a number of specimens. Lipopolysaccharide significantly increased IL-6, IL-8, and PGE2 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 PGE2 but not TNF-alpha and that degenerate disc tissue is more sensitive to a pro-inflammatory stimulus than its scoliotic counterpart.