Investigation of the role of IL-1 and TNF in matrix degradation in the intervertebral disc.
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-1beta, IL-1 receptor antagonist (IL-1Ra), TNF-alpha and anti-TNF.


RESULTS
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.


CONCLUSIONS
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.
Hoyland
J A
JA
Tissue Injury and Repair Group, Research School in Clinical and Laboratory Sciences, Stopford Building, The University of Manchester, Oxford Road, Manchester M13 9PT, UK.
Le Maitre
C
C
Freemont
A J
AJ
D000328:Adult; D000368:Aged; D005109:Extracellular Matrix / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D005260:Female; D006801:Humans; D007375:Interleukin-1 / Q000494:pharmacology / Q000502:physiology*; D007403:Intervertebral Disc / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D008159:Lumbar Vertebrae; D008297:Male; D008666:Metalloendopeptidases / Q000378:metabolism; D008856:Microscopy, Fluorescence; D008875:Middle Aged; D017472:Receptors, Interleukin-1 / Q000037:antagonists & inhibitors; D013122:Spinal Diseases / Q000378:metabolism / Q000473:pathology*; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors / Q000494:pharmacology / Q000502:physiology*
D007375:Interleukin-1; D017472:Receptors, Interleukin-1; D014409:Tumor Necrosis Factor-alpha; D008666:Metalloendopeptidases