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Open Access Research article

MIP-3β/CCL19 is associated with the intrathecal invasion of mononuclear cells in neuroinflammatory and non-neuroinflammatory CNS diseases in dogs

Janina Bartels1, Brett G Darrow2, Scott J Schatzberg3, Lijing Bu4, Regina Carlson1 and Andrea Tipold1*

Author Affiliations

1 Department of Small Animal Medicine and Surgery, University of Veterinary Medicine Hannover, Buenteweg 9, Hannover 30559, Germany

2 Lauderdale Veterinary Specialists, 3217 NW 10th Terrace, Fort Lauderdale, FL, USA

3 VESC Veterinary Emergency and Specialty Center, 2001 Vivigen Way, Santa Fe, NM 87505, USA

4 Biology Department, University of New Mexico, 1 University Boulevard, Northeast, Albuquerque, NM 87131, USA

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BMC Veterinary Research 2014, 10:157  doi:10.1186/1746-6148-10-157

Published: 12 July 2014

Abstract

Background

Chemokines such as MIP-3β/CCL19 are important factors in the mechanism of cell migration and pathogenesis of central nervous system (CNS) inflammatory reactions. The hypothesis of this study is that CCL19, also known as MIP-3β, is involved in the pathogenesis of inflammatory and non-inflammatory CNS diseases of dogs. Experiments were performed on cerebrospinal fluid (CSF) and serum samples of dogs affected with steroid responsive meningitis-arteritis (SRMA) during the acute phase as well as during treatment. Dogs with SRMA were compared to dogs with presumed meningoencephalomyelitis of unknown origin (MUO), and both groups sub-categorized into dogs receiving no therapy and with patients receiving prednisolone therapy. Idiopathic epilepsy (IE), a group with normal CSF cell count, was used as a control. Additionally, dogs with intervertebral disc disease (IVDD) of varying severity were analyzed. Chemokine concentrations were determined by enzyme linked immunosorbent assay. Migration assays were performed on seven selected CSF samples using a disposable 96-well chemotaxis chamber.

Results

CCL19 was detectable in CSF samples of all dogs. Dogs with untreated SRMA and MUO displayed pronounced CCL19 elevations compared to the control group and patients receiving glucocorticosteroid treatment. CSF cell counts of untreated SRMA and MUO patients were significantly positively correlated with the CCL19 CSF concentration. IVDD patients also had elevated CCL19 concentration compared to controls, but values were considerably lower than in inflammatory CNS diseases. Selected CSF samples displayed chemotactic activity for mononuclear cells in the migration assay.

Conclusions

CCL19 CSF concentrations were markedly elevated in patients affected with the neuroinflammatory diseases SRMA and MUO and showed a strong correlation with the CSF cell count. This chemokine may play an important role in the pathogenesis of SRMA and MUO. The elevation of CSF CCL19 in IVDD suggests that it may also be involved in the secondary wave of spinal cord injuries.

Keywords:
Chemokine; MIP-3β/CCL19; Steroid responsive meningitis-arteritis; Meningoencephalomyelitis of unknown origin; Intervertebral disc disease; Chemotaxis