Influence of cytokine inhibitors on concentration and activity of MMP-1 and MMP-3 in disc herniation
IntroductionSpontaneous resorption of disc herniation (DH) after sciatica is well documented and matrix metalloproteinases (MMP)-1 and MMP-3 are involved in this process. Glucocorticoid injections are used for the treatment of sciatica, while tumor necrosis factor (TNF) inhibitors are under investigation.
Little is known about the effect of these drugs on DH resorption.
Methods: DH tissue was harvested from patients undergoing surgery for sciatica. Samples were thoroughly washed.
Diced explants were cultured ex-vivo in 1) 0.5 ml DMEM 10% FCS (controls), 2) recombinant IL-1Ra (100 ng/ ml), 3) dexamethasone (10E-5 M), or 4) TNF inhibitor monoclonal antibody (10 ug/ml). Supernatants were harvested at 48 hours and frozen.
Immunocapture activity assays determined total MMP activity, active MMP levels and pro-MMP levels
Results: Fourteen DH tissue samples were analysed. Levels of all forms of MMP-3 were higher than the respective levels of MMP-1(p<0.01).
In particular, the median (IQR) total MMP-3 level was 0.97 (0.47 - 2.19) ng/mg of tissue compared to 0.024 (0.01 - 0.07) ng/mg of total MMP-1 level (p<0.01). Incubation with IL-1Ra, dexamethasone, or TNF inhibitors significantly decreased levels of all forms of MMP-3 (p<0.05).
Dexamethasone significantly decreased the ratio of active MMP-3 to total MMP-3 activity. A significant inhibitory effect of dexamethasone was observed only on active MMP-1, while IL-1 and TNF inhibitors had no significant effect on any form of MMP-1.
Conclusions: MMP-3 appears to play a greater role than MMP-1 in DH resorption.
Dexamethasone, IL-1Ra and TNF inhibitor decreased active MMP-3, indicating that the clinical use of these drugs may affect the resorption of DH under certain conditions.
Author: Stephane GenevayAxel FinckhFrancoise MezinEnrico TessitorePierre-Andre Guerne
Credits/Source: Arthritis Research &Therapy 2009, 11:R169
Published on: 2009-11-11
Copyright by the authors listed above - made available via BioMedCentral (Open Access). Please
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