• Editorial
• Open Access

A better understanding of the pathogenesis of inflammatory arthritis has led to the development and subsequent successful use in humans of biopharmaceuticals blocking, for example, tumor necrosis factor (TNF)α, CD-20, IL-1 and IL-6 and T-cell co-stimulating factors (CTLA-4). No targeted treatments are available, however, for degenerative rheumatological diseases such as low back pain (LBP) due to intervertebral disc (IVD) degeneration or knee osteoarthritis (OA). This deficiency may be due in part to our limited understanding of the pathogenesis of these diseases; a better understanding of the pathogenesis of IVD degeneration is a prerequisite for developing successful biological therapeutic approaches for patients with LBP.

Current work presented by Freemont's group [1] has contributed greatly to our understanding of disc remodeling in degenerative IVD, notably the role of pro-inflammatory cytokines. They compare the expression of IL-1β and TNFα as well as their main functional receptors in human IVDs [1]. The most important aspect of this study is the comparison of non-degenerated, degenerated and herniated samples of human IVDs. In non-degenerated human IVDs, both cytokines were expressed at low levels, with an increase in IL-1β compared to TNFα and a low level of cells positive for TNF receptor type I [1]. In degenerated human IVDs, although the protein production of the two cytokines was increased compared with the non-degenerated samples, the number of positive cells and the level of gene expression was greater for IL-1β than for TNFα. Furthermore, IL-1 RI gene expression and protein production were also increased in degenerated compared with non-degenerated samples, and a tendency for decreased synthesis of TNF RI was even observed in herniated and degenerated human IVDs compared to non-degenerated samples. These results are very important because they suggest that IL-1β is more predominant in the process of IVD degeneration than TNFα [2]. However, they do not explain the exact roles of both cytokines and raise more questions than they answer. How do the effects of TNFα and IL-1β combine to alter the extracellular matrix of discs? Do they act in the same way in degenerated and herniated IVDs? Do they act in the same time period? Are both cytokines involved in pain generation? What is the role of IL-1α?

These data suggest that IL-1β could be a valid target for inhibiting disc degeneration and offer an exciting challenge for developing future therapeutic approaches. Among IL-1 inhibitors, IL-1 receptor antagonist (IL-1ra) might be a candidate for preventing IVD degeneration [3]. Indeed, Freemont and colleagues have shown in monolayer and three-dimensional alginate-cultured resident cells from degenerate IVDs that IL-1ra down-regulates metal-dependent proteases [4] and, delivered directly or by gene therapy in explants of degenerated human IVDs, almost completely eliminates enzyme activity, thereby decreasing extracellular matrix degradation [2].