IN VITRO INVESTIGATION OF CYTOKINE-MEDIATED NUCLEUS PULPOSUS DEGENERATION NSF Summer Undergraduate Fellowship in Sensor Technologies

Degeneration of the lumbar intervertebral discs is strongly implicated as a cause of low back pain, and may also lead to impaired mobility. A lack of understanding of the pathomechanisms that underlie degeneration limits our ability to develop biological treatments that both alleviate painful symptoms and restore function. The process of degeneration is characterized by up-regulation of pro-inflammatory cytokines—particularly interleukin 1 beta (IL1β) and tumor necrosis factor alpha (TNFα)—within the central nucleus pulposus. Furthermore, the increased production of these cytokines is not matched by increasing amounts of their inhibitory regulators, resulting in an imbalance of catabolic and anabolic activity. In this study, we developed an in-vitro model of the nucleus pulposus that was used to investigate the effects of IL1β and TNFα on composition and mechanical function. In addition, we examined the capacity of IL1 receptor antagonist (IL1ra) and soluble TNF receptor 1 (sTNFR1), inhibitors of IL1β and TNFα respectively, to mitigate cytokine-mediated functional and compositional changes. Our results demonstrated that short-term exposure to IL1β, but not TNFα, causes loss of matrix components that significantly compromises mechanical function, suggesting that IL1β plays a more direct role than TNFα in driving matrix degradation in the nucleus pulposus. Our results also demonstrated that IL1ra can effectively prevent compositional and functional changes induced by IL1β, highlighting its therapeutic potential.