Philemon Karli1, Valentine Martlé2, Kenny Bossens2, Artur Summerfield3, Marcus G Doherr4, Paul Turner5, Marc Vandevelde6, Franck Forterre7, Diana Henke6. 1. 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. 2. Department of Small Animal Medicine and Clinical Biology, Faculty of Veterinary Medicine, Ghent University, Salisburylaan 133, 9820 Merelbeke, Belgium. 3. Research Department, Institute of Virology and Immunoprophylaxis (IVI), Sensemattstrasse 293, 3147 Mittelhäusern, Switzerland. 4. Department of Clinical Research and Veterinary Public Health, Vetsuisse Faculty, University of Bern, Länggassstrasse 128, Bern CH-3001, Switzerland. 5. Affymetrix UK Ltd, Voyager, Mercury Park, Wycombe Lane, Wooburn Green, High Wycombe HP10 0HH, UK. 6. Division of Neurological Sciences, Department of Clinical Veterinary Neurology, Vetsuisse Faculty, University of Bern, Länggassstrasse 128, Bern CH-3001, Switzerland. 7. Division of Clinical Surgery, Department of Clinical Veterinary Medicine, Vetsuisse Faculty, University of Bern, Länggassstrasse 128, Bern CH-3001, Switzerland.
Abstract
BACKGROUND CONTEXT: In canine intervertebral disc (IVD) disease, a useful animal model, only little is known about the inflammatory response in the epidural space. PURPOSE: To 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/ SETTING: Prospective study using extruded IVD material of dogs with thoracolumbar IVD extrusion. PATIENT SAMPLE: Seventy affected and 13 control (24 samples) dogs. OUTCOME MEASURES: Duration of neurologic signs, pretreatment, neurologic grade, severity of pain, and outcome were recorded. After diagnostic imaging, decompressive surgery was performed. METHODS: Messenger 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. RESULTS: Fold 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). CONCLUSIONS: The 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.
BACKGROUND CONTEXT: In canineintervertebral disc (IVD) disease, a useful animal model, only little is known about the inflammatory response in the epidural space. PURPOSE: To 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/ SETTING: Prospective study using extruded IVD material of dogs with thoracolumbar IVD extrusion. PATIENT SAMPLE: Seventy affected and 13 control (24 samples) dogs. OUTCOME MEASURES: Duration of neurologic signs, pretreatment, neurologic grade, severity of pain, and outcome were recorded. After diagnostic imaging, decompressive surgery was performed. METHODS: Messenger 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. RESULTS: Fold 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). CONCLUSIONS: The 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 canineIVD disease model will be rewarding in this process.
Authors: Nicole Willems; Anna R Tellegen; Niklas Bergknut; Laura B Creemers; Jeannette Wolfswinkel; Christian Freudigmann; Karin Benz; Guy C M Grinwis; Marianna A Tryfonidou; Björn P Meij Journal: BMC Vet Res Date: 2016-01-13 Impact factor: 2.741
Authors: D Mayer; A Oevermann; T Seuberlich; M Vandevelde; A Casanova-Nakayama; S Selimovic-Hamza; F Forterre; D Henke Journal: J Vet Intern Med Date: 2016-06-29 Impact factor: 3.333
Authors: Sara Hanaei; Sina Abdollahzade; Maryam Sadr; Mohammad Hossein Mirbolouk; Ehsan Fattahi; Alireza Khoshnevisan; Nima Rezaei Journal: BMC Med Genet Date: 2020-07-03 Impact factor: 2.103