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

Rheumatology (Oxford). 2008 Jun;47(6):809-14. doi: 10.1093/rheumatology/ken056. Epub 2008 Apr 8.

Abstract

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.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Extracellular Matrix / drug effects
  • Extracellular Matrix / metabolism
  • Extracellular Matrix / pathology*
  • Female
  • Humans
  • Interleukin-1 / pharmacology
  • Interleukin-1 / physiology*
  • Intervertebral Disc / drug effects
  • Intervertebral Disc / metabolism
  • Intervertebral Disc / pathology*
  • Lumbar Vertebrae
  • Male
  • Metalloendopeptidases / metabolism
  • Microscopy, Fluorescence
  • Middle Aged
  • Receptors, Interleukin-1 / antagonists & inhibitors
  • Spinal Diseases / metabolism
  • Spinal Diseases / pathology*
  • Tumor Necrosis Factor-alpha / antagonists & inhibitors
  • Tumor Necrosis Factor-alpha / pharmacology
  • Tumor Necrosis Factor-alpha / physiology*

Substances

  • Interleukin-1
  • Receptors, Interleukin-1
  • Tumor Necrosis Factor-alpha
  • Metalloendopeptidases