Investigation of the role of IL-1 and TNF in matrix degradation in the intervertebral disc.

Abstract

To establish if IL-1 or TNF regulates matrix degradation in the non-degenerate or degenerate intervertebral disc (IVD). In situ zymography (ISZ) has been used to investigate the role of IL-1 and TNF in the matrix degradation characterizing symptomatic IVD degeneration. ISZ employed three substrates (gelatin, collagen II, casein) and four different challenges, IL-1beta, IL-1 receptor antagonist (IL-1Ra), TNF-alpha and anti-TNF. We have shown for the first time that whilst IL-1beta will stimulate and IL-1 receptor antagonist will inhibit matrix degradation in intact human IVD tissue, neither TNF-alpha nor anti-TNF have any measurable effect on degradation of these matrices. This study has addressed a current area of controversy in IVD biology, namely, whether either IL-1 or TNF or both are involved in driving matrix degradation. Our data indicate that IL-1 is a key cytokine mediating matrix degradation in the IVD and therefore a therapeutic target.