Cytokines and chemokines in the pathogenesis of low back pain

Degeneration of the intervertebral disc (IVD) is thought to account for 40% of all cases of chronic low back pain. Alterations in the behaviour of the IVDs’ native cell population mediate the processes that lead to structural failure, as seen in IVD degeneration. Cytokines are implicated in this process, several studies have identified that Interleukin-1 (IL-1) and Tumour Necrosis Factor-α (TNF-α) expression is increased in degenerate IVDs compared to their normal counterparts. Furthermore, it has been shown in vitro that these cytokines stimulate alterations in the behaviour of the IVDs’ native cells in a similar manner to those observed in IVD degeneration. However, IL-1 and TNF-α are only two of a large group of intercellular signalling molecules known as cytokines, and studies investigating the expression of other cytokines in the human IVD are limited. This thesis demonstrates the production of numerous cytokines and chemokines (chemoattractant cytokines) by the human IVDs’ native cell population. Detailed gene and protein expression studies identified several novel cytokines and chemokines that are differentially expressed in cells isolated from degenerate or prolapsed IVDs compared to those isolated from the normal counterpart. Coexpression of receptors for these molecules was also identified, indicating a capacity of these cells to respond to cytokine intercellular signalling. The response of IVD cells to cytokine and chemokine stimulation in vitro was investigated. The data presented indicates that inter-regulatory relationships exist between the cytokines and chemokines of the intervertebral disc. Particularly, IL-1 exerts modulatory potential over the expression of other cytokines and chemokines by IVD cells. Effects of stimulation were also observed in relation to reduced anabolic metabolism and increased catabolic metabolism, both of which are characteristic features of IVD degeneration. Together, the findings presented in this thesis indicate that cytokines and chemokines are integral to the pathogenesis of IVD degeneration and prolapse that may lead to low back pain.