Capability of Nondegenerated and Degenerated Discs in Producing Inflammatory Agents With or Without Macrophage Interaction

Study Design. Molecular biological and immunohistological examinations. Objective. To clarify whether nondegenerated and degenerated discs produce inflammatory agents such as prostaglandin (PG)E2, interleukin (IL)-6, IL-1 beta, and tumor necrosis factor (TNF)alpha, which have been reported to play pivotal roles in lumbar disc diseases, in the presence or absence of macrophages. Summary of Background Data. A recent study reported discogenic low back pain might be caused by annular disruption followed by vascularized granulation formation extending from the outer layer of the annulus fibrosus into the nucleus pulposus along the torn fissure. Moreover, abundant macrophages have been shown to be present in symptomatic discs but not in normal and aged discs. However, there has been no in vitro report investigating the interaction between macrophages and several degrees of degenerated discs. Methods. Degenerated intervertebral discs were obtained from Sprague-Dawley rats with different lengths of rat tail compression (2, 4, and 8 weeks). These degenerated disc and nondegenerated disc tissues were respectively cultured in the presence or absence of macrophages. The culture supernatants were analyzed for PGE2, IL-6, IL-1 beta, and TNF-alpha. Immunohistochemical staining for cyclooxygenase-2 and IL-6 was also carried out on 4-week compression discs. Results. Nondegenerated discs alone, several degrees of degenerated discs alone, and macrophages alone produced small amounts of PGE2 and IL-6. However, they were able to produce significantly higher amounts of PGE2 and IL-6 when cocultured with macrophages. In contrast, we detected small amounts of IL-1 beta and TNF-alpha at every stage of degeneration regardless of the presence or absence of macrophages. The immunohistological examination showed anticyclooxygenase-2 and anti-IL-6 reactivities in the chondrocytes embedded in the disc matrix obtained from the degenerated disc. Conclusion. These results suggest PGE2 and IL-6 play a pivotal role in the interaction between degenerated discs and macrophages.