• Philemon Karli, Valentine Martlé, Kenny Bossens, Artur Summerfield, Marcus G Doherr, Paul Turner, Marc Vandevelde, Franck Forterre, and Diana Henke.
• Division of Neurological Sciences, Department of Clinical Veterinary Neurology, Vetsuisse Faculty, University of Bern, Länggassstrasse 128, Bern CH-3001, Switzerland. Electronic address: philemon.karli@vetsuisse.unibe.ch.
• Spine J. 2014 Dec 1;14(12):2976-84.

Background ContextIn canine intervertebral disc (IVD) disease, a useful animal model, only little is known about the inflammatory response in the epidural space.PurposeTo determine messenger RNA (mRNA) expressions of selected cytokines, chemokines, and matrix metalloproteinases (MMPs) qualitatively and semiquantitatively over the course of the disease and to correlate results to neurologic status and outcome.Study Design/SettingProspective study using extruded IVD material of dogs with thoracolumbar IVD extrusion.Patient SampleSeventy affected and 13 control (24 samples) dogs.Outcome MeasuresDuration of neurologic signs, pretreatment, neurologic grade, severity of pain, and outcome were recorded. After diagnostic imaging, decompressive surgery was performed.MethodsMessenger RNA expressions of interleukin (IL)-1β, IL-2, IL-4, IL-6, IL-8, IL-10, tumor necrosis factor (TNF), interferon (IFN)γ, MMP-2, MMP-9, chemokine ligand (CCL)2, CCL3, and three housekeeping genes was determined in the collected epidural material by Panomics 2.0 QuantiGene Plex technology. Relative mRNA expression and fold changes were calculated. Relative mRNA expression was correlated statistically to clinical parameters.ResultsFold changes of TNF, IL-1β, IL-2, IL-4, IL-6, IL-10, IFNγ, and CCL3 were clearly downregulated in all stages of the disease. MMP-9 was downregulated in the acute stage and upregulated in the subacute and chronic phase. Interleukin-8 was upregulated in acute cases. MMP-2 showed mild and CCL2 strong upregulation over the whole course of the disease. In dogs with severe pain, CCL3 and IFNγ were significantly higher compared with dogs without pain (p=.017/.020). Dogs pretreated with nonsteroidal anti-inflammatory drugs revealed significantly lower mRNA expression of IL-8 (p=.017).ConclusionsThe high CCL2 levels and upregulated MMPs combined with downregulated T-cell cytokines and suppressed pro-inflammatory genes in extruded canine disc material indicate that the epidural reaction is dominated by infiltrating monocytes differentiating into macrophages with tissue remodeling functions. These results will help to understand the pathogenic processes representing the basis for novel therapeutic approaches. The canine IVD disease model will be rewarding in this process.Copyright © 2014 Elsevier Inc. All rights reserved.

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