title: Inflammatory profiles in canine intervertebral disc degeneration.
abstract: BACKGROUND
  Intervertebral disc (IVD) disease is a common spinal disorder in dogs and degeneration and inflammation are significant components of the pathological cascade. Only limited studies have studied the cytokine and chemokine profiles in IVD degeneration in dogs, and mainly focused on gene expression. A better understanding is needed in order to develop biological therapies that address both pain and degeneration in IVD disease. Therefore, in this study, we determined the levels of prostaglandin E2 (PGE2), cytokines, chemokines, and matrix components in IVDs from chondrodystrophic (CD) and non-chondrodystrophic (NCD) dogs with and without clinical signs of IVD disease, and correlated these to degeneration grade (according to Pfirrmann), or herniation type (according to Hansen). In addition, we investigated cyclooxygenase 2 (COX-2) expression and signs of inflammation in histological IVD samples of CD and NCD dogs.
  
  
  RESULTS
  PGE2 levels were significantly higher in the nucleus pulposus (NP) of degenerated IVDs compared with non-degenerated IVDs, and in herniated IVDs from NCD dogs compared with non-herniated IVDs of NCD dogs. COX-2 expression in the NP and annulus fibrosus (AF), and proliferation of fibroblasts and numbers of macrophages in the AF significantly increased with increased degeneration grade. GAG content did not significantly change with degeneration grade or herniation type. Cytokines interleukin (IL)-2, IL-6, IL-7, IL-8, IL-10, IL-15, IL-18, immune protein (IP)-10, tumor necrosis factor (TNF)-α, and granulocyte macrophage colony-stimulating factor (GM-CSF) were not detectable in the samples. Chemokine (C-C) motif ligand (CCL)2 levels in the NP from extruded samples were significantly higher compared with the AF of these samples and the NP from protrusion samples.
  
  
  CONCLUSIONS
  PGE2 levels and CCL2 levels in degenerated and herniated IVDs were significantly higher compared with non-degenerated and non-herniated IVDs. COX-2 expression in the NP and AF and reactive changes in the AF increased with advancing degeneration stages. Although macrophages invaded the AF as degeneration progressed, the production of inflammatory mediators seemed most pronounced in degenerated NP tissue. Future studies are needed to investigate if inhibition of PGE2 levels in degenerated IVDs provides effective analgesia and exerts a protective role in the process of IVD degeneration and the development of IVD disease.
authors.affiliation: Department of Clinical Sciences of Companion Animals, Faculty of Veterinary Medicine, 3584 CM, Utrecht, The Netherlands.
authors.forename: Nicole
authors.initials: N
authors.lastname: Willems
authors.affiliation: Department of Clinical Sciences of Companion Animals, Faculty of Veterinary Medicine, 3584 CM, Utrecht, The Netherlands.
authors.forename: Anna R
authors.initials: AR
authors.lastname: Tellegen
authors.affiliation: Department of Clinical Sciences of Companion Animals, Faculty of Veterinary Medicine, 3584 CM, Utrecht, The Netherlands.
authors.forename: Niklas
authors.initials: N
authors.lastname: Bergknut
authors.affiliation: Department of Orthopaedics, University Medical Center, 3584 CX, Utrecht, The Netherlands.
authors.forename: Laura B
authors.initials: LB
authors.lastname: Creemers
authors.affiliation: Department of Clinical Sciences of Companion Animals, Faculty of Veterinary Medicine, 3584 CM, Utrecht, The Netherlands.
authors.forename: Jeannette
authors.initials: J
authors.lastname: Wolfswinkel
authors.affiliation: NMI Natural and Medical Sciences Institute at the University of Tuebingen, Regenerative Medicine II, 72770, Reutlingen, Germany.
authors.forename: Christian
authors.initials: C
authors.lastname: Freudigmann
authors.affiliation: NMI Natural and Medical Sciences Institute at the University of Tuebingen, Regenerative Medicine II, 72770, Reutlingen, Germany.
authors.forename: Karin
authors.initials: K
authors.lastname: Benz
authors.affiliation: Department of Pathobiology, Faculty of Veterinary Medicine, 3508 TD, Utrecht, The Netherlands.
authors.forename: Guy C M
authors.initials: GC
authors.lastname: Grinwis
authors.affiliation: Department of Clinical Sciences of Companion Animals, Faculty of Veterinary Medicine, 3584 CM, Utrecht, The Netherlands. m.a.tryfonidou@uu.nl.
authors.forename: Marianna A
authors.initials: MA
authors.lastname: Tryfonidou
authors.affiliation: Department of Clinical Sciences of Companion Animals, Faculty of Veterinary Medicine, 3584 CM, Utrecht, The Netherlands.
authors.forename: Björn P
authors.initials: BP
authors.lastname: Meij
mesh_terms: D000818:Animals; D051546:Cyclooxygenase 2 / Q000096:biosynthesis; D004283:Dog Diseases / Q000097:blood / Q000473:pathology*; D004285:Dogs; D005109:Extracellular Matrix / Q000378:metabolism; D018836:Inflammation Mediators / Q000097:blood*; D055959:Intervertebral Disc Degeneration / Q000097:blood / Q000473:pathology / Q000662:veterinary*; D007405:Intervertebral Disc Displacement / Q000097:blood / Q000473:pathology / Q000662:veterinary*; D010009:Osteochondrodysplasias / Q000473:pathology / Q000662:veterinary
chemical_list: D018836:Inflammation Mediators; D051546:Cyclooxygenase 2