title: Serum levels of innate immunity cytokines are elevated in dogs with metaphyseal osteopathy (hypertrophic osteodytrophy) during active disease and remission.
abstract: Metaphyseal osteopathy (MO) (hypertrophic osteodystrophy) is a developmental disorder of unexplained etiology affecting dogs during rapid growth. Affected dogs experience relapsing episodes of lytic/sclerotic metaphyseal lesions and systemic inflammation. MO is rare in the general dog population; however, some breeds (Weimaraner, Great Dane and Irish Setter) have a much higher incidence, supporting a hereditary etiology. Autoinflammatory childhood disorders of parallel presentation such as chronic recurrent multifocal osteomyelitis (CRMO), and deficiency of interleukin-1 receptor antagonist (DIRA), involve impaired innate immunity pathways and aberrant cytokine production. Given the similarities between these diseases, we hypothesize that MO is an autoinflammatory disease mediated by cytokines involved in innate immunity. To characterize immune dysregulation in MO dogs we measured serum levels of inflammatory markers in 26 MO and 102 control dogs. MO dogs had significantly higher levels (pg/ml) of serum Interleukin-1beta (IL-1β), IL-18, IL-6, Granulocyte-macrophage colony stimulating factor (GM-CSF), C-X-C motif chemokine 10 (CXCL10), tumor necrosis factor (TNF), and IL-10. Notably, recovered MO dogs were not different from dogs during active MO disease, providing a suggestive mechanism for disease predisposition. This is the first documentation of elevated immune markers in MO dogs, uncovering an immune profile similar to comparable autoinflammatory disorders in children.
authors: School of Veterinary Medicine, University of California, Davis, 1 Garrod Drive, Davis, CA 95616, USA. Electronic address: nsafra@ucdavis.edu.
authors: Noa
authors: N
authors: Safra
authors: School of Veterinary Medicine, University of California, Davis, 1 Garrod Drive, Davis, CA 95616, USA; Swedish University of Agricultural Sciences, Almas Allé 8, 750 07 Uppsala, Sweden.
authors: Peta L
authors: PL
authors: Hitchens
authors: Department of Dermatology, University of California, Davis, 3301 C Street, Sacramento, CA 95816, USA.
authors: Emanual
authors: E
authors: Maverakis
authors: Department of Dermatology, University of California, Davis, 3301 C Street, Sacramento, CA 95816, USA.
authors: Anupam
authors: A
authors: Mitra
authors: School of Veterinary Medicine, University of California, Davis, 1 Garrod Drive, Davis, CA 95616, USA.
authors: Courtney
authors: C
authors: Korff
authors: School of Veterinary Medicine, University of California, Davis, 1 Garrod Drive, Davis, CA 95616, USA.
authors: Eric
authors: E
authors: Johnson
authors: School of Veterinary Medicine, University of California, Davis, 1 Garrod Drive, Davis, CA 95616, USA.
authors: Amir
authors: A
authors: Kol
authors: School of Veterinary Medicine, University of California, Davis, 1 Garrod Drive, Davis, CA 95616, USA.
authors: Michael J
authors: MJ
authors: Bannasch
authors: School of Veterinary Medicine, University of California, Davis, 1 Garrod Drive, Davis, CA 95616, USA.
authors: Niels C
authors: NC
authors: Pedersen
authors: School of Veterinary Medicine, University of California, Davis, 1 Garrod Drive, Davis, CA 95616, USA.
authors: Danika L
authors: DL
authors: Bannasch
mesh_terms: D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology; D001848:Bone Diseases, Developmental / Q000276:immunology / Q000662:veterinary*; D016207:Cytokines / Q000097:blood*; D004283:Dog Diseases / Q000276:immunology*; D004285:Dogs; D005260:Female; D007113:Immunity, Innate; D008297:Male
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D016207:Cytokines
keywords: Autoinflammatory; Canine; Cytokines; Hypertrophic osteodystrophy; Innate immunity