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In canine intervertebral disc (IVD) disease, a useful animal model, only little is known about the inflammatory response in the epidural space.
To determine mRNA expression of selected cytokines, chemokines and matrix metalloproteinases (MMP) qualitatively and semi-quantitatively over the course of the disease and to correlate results to neurological status and outcome.
Prospective study using extruded IVD material of dogs with thoracolumbar IVD extrusion.
Seventy affected and 13 control (24 samples) dogs.
Duration of neurological signs, pre-treatment, neurological grade, severity of pain, and outcome were recorded. Following diagnostic imaging, decompressive surgery was performed.
mRNA expression of interleukin (IL)-1β, IL-2, IL-4, IL-6, IL-8, IL-10, TNF (tumor necrosis factor), IFN (interferon)γ, MMP-2, MMP-9, CCL (chemokine ligand)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. The study was funded by the Specialization-commission of the University of Bern, Burgergemeinde Bern, and Novartis (Basel). The authors report no conflicts of interest related to this study.
Fold changes of TNF, IL-1β, IL-2, IL-4, IL-6, IL-10, IFNγ, CCL3 were clearly down-regulated in all stages of the disease. MMP-9 was down-regulated in the acute stage and up-regulated in the subacute and chronic phase. IL-8 was up-regulated in acute cases. MMP-2 showed mild and CCL2 strong up-regulation over the whole course of the disease. In dogs with severe pain, CCL3 and IFNγ were significantly higher compared to dogs without pain (p=0.017/0.020). Dogs pre-treated with non-steroidal anti-inflammatory drugs revealed significantly lower mRNA expression of IL-8 (p=0.017).
The high CCL2 levels and up-regulated MMP's combined with down-regulated T-cell cytokines and suppressed pro-inflammatory genes in extruded canine disc material indicates 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 IVDD model will be rewarding in this process.