Catabolic cytokine expression in degenerate and herniated human intervertebral discs: IL-1 beta and TNF alpha expression profile.

ABSTRACT: Low back pain is a common and debilitating disorder. Current evidence implicates intervertebral disc (IVD) degeneration and herniation as major causes, although the pathogenesis is poorly understood. While several cytokines have been implicated in the process of IVD degeneration and herniation investigations have predominately focused on IL-1 and TNF alpha. However, to date no studies have investigated the expression of these cytokines simultaneously in IVD degeneration or herniation, or determined which may be the predominant cytokine associated with these disease states. Using quantitative real time PCR and immunohistochemistry we investigated gene and protein expression for IL-1 beta, TNF alpha and their receptors in non-degenerate, degenerate and herniated human IVDs. IL-1 beta gene expression was observed in a greater proportion of IVDs than TNF alpha (79% v/s 59%). Degenerate and herniated IVDs displayed higher levels of both cytokines than non-degenerate IVDs, although in degenerate IVDs higher levels of IL-1 beta gene expression (1300 copies/100ng cDNA) were observed compared to levels of TNF alpha (250 copies of TNF alpha/100ng/cDNA). Degenerate IVDs showed 10 fold higher IL-1 receptor gene expression compared to non-degenerate IVDs. In addition 80% of degenerate IVD cells displayed IL-1 receptor immunopositivity compared to only 30% of cells in non-degenerate IVDs. However no increase in TNF receptor I gene or protein expression was observed in degenerate or herniated IVDs compared to non-degenerate IVDs. We have demonstrated that although both cytokines are produced by human IVD cells, IL-1 beta is expressed at higher levels and in more IVDs, particularly in more degenerate IVDs (grades 4-12). Importantly this study has highlighted an increase in gene and protein production for the IL-1 RI but not TNF RI in degenerate IVDs. The data thus suggests that although both cytokines may be involved in the pathogenesis of IVD degeneration, IL-1 may have a more significant role than TNF alpha, and thus may be a better target for therapeutic intervention.