All authors reviewed and approved the final manuscript. == Contributor Information == Stphane Genevay, Email: stephane.genevay@hcuge.ch. Axel Finckh, Email: axel.finckh@hcuge.ch. Franoise Mezin, Email: f.mezin1@orange.fr. Enrico Tessitore, Email: enrico.tessitore@hcuge.ch. Pierre-Andr Guerne, Email: pierre-andre.guerne@hcuge.ch. == Acknowledgements == The authors are grateful to Pascale Sclison for her help in editing the manuscript, and to theCentre de Recherches Mdicales Carlos & Elsie de Reuter for its financial support. == References ==. 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 inhibitor had no significant LY2608204 effect LY2608204 on any form. == Conclusions == MMP-3 appears LY2608204 to play a greater role than MMP-1 in DH resorption. Dexamethasone, IL-1-Ra and TNF inhibitor decreased active MMP-3, indicating that the clinical use of these drugs may affect the resorption of DH under certain conditions. == Introduction == Disc herniation (DH) is classically described as the protrusion of degenerated disc tissue within the spinal canal [1]. Although DH is found in many asymptomatic subjects, lumbar DH is associated with radicular leg pain syndrome often referred to as sciatica. While sciatica was long thought to result only from mechanical compression of the nerve root, recent studies have underlined the importance of inflammation and cytokines in this process. Partly for this reason, glucocorticoids [2] and, more recently, TNF inhibitors [3,4] were introduced in the treatment of sciatica. The usual clinical evolution of sciatica is toward recovery with resolution of leg pain. Reduction in clinical symptoms has been shown to be correlated with a reduction of DH size on subsequent magnetic resonance imaging [5]. Matrix metalloproteinases (MMPs) are a group of over 20 zinc-dependent enzymes that catalyze the degradation of protein components of the extracellular matrix. MMPs therefore contribute to the tissue resorption and remodeling of the extracellular matrix that occur in reaction to tissue degeneration [6]. MMP-1 (collagease-1) and MMP-3 (stromelysin-1) are known to be involved in the turnover of normal tissue but also in its pathological degradation. Osteoarthritis [7,8], spondyloarthropathy [9] or intervertebral disc (IVD) degeneration [10] illustrates this process. MMPs have also been shown to be increased in DH tissue compared with that of healthy IVDs [11] and participate in DH degradation and resorption after an episode of sciatica [12]. Little information is available, however, on their respective importance in this process. Synthesized as inactive pro-zymogens, MMPs go through a post-transcriptional process of cleavage and activation, enabling the targeted degradation of their substrate. The regulation of MMP activity is a complex and finely tuned process in which both specific inhibitors (tissue inhibitors of metalloproteinases) and the regulation of afferent pathways at production and activation levels play an important part. Inflammatory cytokines such as IL-1 and TNF are thought to contribute to these regulatory processes [7]. The use of glucocorticoids [2] and TNF inhibitors [3,4] in the treatment of sciatica might therefore hinder DH resorption and, possibly, the median or long-term evolution KLK7 antibody of the disease. The goal of the present study was therefore to investigate the effects of glucocortiocoids (dexamethasone) and specific cytokine inhibitors (IL-1Ra and anti-TNF antibody) on levels of MMP-1 and MMP-3 in DH. We used assays that distinguish active enzymes from inactive enzymes to partially address the level of regulation at which these drugs might be active. == Materials and methods == The local research ethics committee’s approval was given for the work. DH tissues were obtained after informed consent from 14 patients undergoing surgical lumbar discectomy for persistent radicular symptoms. No patients.
