Inflammatory Processes Associated with Canine Intervertebral Disc Herniation.

Monchaux-Azmanis, Marie Paula Suzanne Minna; Forterre, Simone; Spreng, David; Karol, Agnieszka; Forterre, Franck; Wuertz-Kozak, Karin (2017). Inflammatory Processes Associated with Canine Intervertebral Disc Herniation. Frontiers in immunology, 8(1681), p. 1681. Frontiers Research Foundation 10.3389/fimmu.2017.01681

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Intervertebral disc herniation (IVDH) is an important pathology in humans and also in dogs. While the molecular disease mechanisms are well investigated in humans, little is known about the inflammatory mediators in naturally occurring canine IVDH. The objective of this study was to investigate whether the involved proinflammatory cytokines in human IVDH are also key cytokines in canine IVDH and thus to elucidate the suitability of the dog as a model for human trials. 59 samples from 25 dogs with surgically confirmed thoracolumbar IVDH were collected and classified in three subgroups: herniated (H), affected non-herniated (NH) disc, and adjacent non-affected (NA) disc. Discs from 11 healthy dogs acted as controls (C). Samples were analyzed for IL-1, IL-6, IL-8, and TNF-α expression (qPCR/ELISA) as well as cell infiltration and activation of the MAP kinase pathways (immunohistochemistry). Gene and protein expression of all key cytokines could be detected in IVDH affected dogs. Canine IVDH was significantly associated with a higher gene expression of IL-6 (H > C, NH > C) and TNF-α (H > C, NH > C, NA > C) and a significant down-regulation of IL-1β (H < C). Dogs with spontaneous pain had significantly higher IL-6 mRNA compared to those with pain arising only upon palpation. An inter-donor comparison (H and HN relative to NA) revealed a significant increase of IL-6 gene expression (H > NA, NH > NA). IL-8 (H > C, NA > C) and TNF-α (NH > C) protein levels were significantly increased in diseased dogs while inversely, IL-6 protein levels were significantly higher in patients with better clinical outcome. Aside from resident IVD cells, mostly monocytes and macrophages were found in extruded material, with concomitant activation of extracellular signal-regulated kinase p38 in the majority of samples. Dogs with spontaneous IVDH might provide a useful model for human disc diseases. Although the expression of key cytokines found in human IVDH was also demonstrated in canine tissue, the inflammatory mechanisms accompanying canine IVDH diverges partially from humans, which will require further investigations in the future. In dogs, IL-6 seems to play an important pathological role and may represent a new potential therapeutic target for canine patients.

Item Type:

Journal Article (Original Article)

Division/Institute:

05 Veterinary Medicine > Department of Clinical Veterinary Medicine (DKV) > Small Animal Clinic
05 Veterinary Medicine > Department of Clinical Veterinary Medicine (DKV)
05 Veterinary Medicine > Department of Clinical Veterinary Medicine (DKV) > Small Animal Clinic > Small Animal Clinic, Surgery

UniBE Contributor:

Monchaux-Azmanis, Marie Paula Suzanne Minna; Forterre, Simone; Spreng, David and Forterre, Franck

Subjects:

600 Technology > 630 Agriculture
600 Technology > 610 Medicine & health

ISSN:

1664-3224

Publisher:

Frontiers Research Foundation

Language:

English

Submitter:

Simone Forterre

Date Deposited:

20 Apr 2018 15:19

Last Modified:

25 Oct 2019 07:45

Publisher DOI:

10.3389/fimmu.2017.01681

PubMed ID:

29255462

Uncontrolled Keywords:

IL-1β IL-6 IL-8 MAP kinase pathway TNF-α canine animal model inflammatory mediators intervertebral disc herniation

BORIS DOI:

10.7892/boris.108830

URI:

https://boris.unibe.ch/id/eprint/108830

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