Rheumatology Advance Access originally published online on April 8, 2008
Rheumatology 2008 47(6):809-814; doi:10.1093/rheumatology/ken056
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Investigation of the role of IL-1 and TNF in matrix degradation in the intervertebral disc
Tissue Injury and Repair Group, Research School of Clinical and Laboratory Sciences, The University of Manchester, Manchester, UK.
Correspondence to: A. J. Freemont, Tissue Injury and Repair Group, Research School in Clinical and Laboratory Sciences, Stopford Building, The University of Manchester, Oxford Road, Manchester M13 9PT, UK. E-mail: tony.freemont{at}manchester.ac.uk
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Abstract |
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Objective. To establish if IL-1 or TNF regulates matrix degradation in the non-degenerate or degenerate intervertebral disc (IVD).
Methods. 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-1β, IL-1 receptor antagonist (IL-1Ra), TNF-
and anti-TNF.
Results. We have shown for the first time that whilst IL-1β will stimulate and IL-1 receptor antagonist will inhibit matrix degradation in intact human IVD tissue, neither TNF- nor anti-TNF have any measurable effect on degradation of these matrices.
Conclusion. 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.
KEY WORDS: Intervertebral disc, Interleukin-1, Interleukin-1Ra, Tumour necrosis factor, In situ zymography, Matrix degradation
Submitted 6 August 2007;
revised version accepted 24 January 2008.
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