Abstract
BackgroundChemokines 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.ResultsCCL19 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.ConclusionsCCL19 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.
Highlights
Chemokines such as Macrophage inflammatory protein-3beta (MIP-3β)/C-C motif ligand 19 (CCL19) are important factors in the mechanism of cell migration and pathogenesis of central nervous system (CNS) inflammatory reactions
There were significant differences detected between samples from dogs with Idiopathic epilepsy (IE) and from healthy animals, IE is considered as the control group due to normal cerebrospinal fluid (CSF) examinations and normal CSF
Since only a small number of neurologically normal dogs was available for evaluation, further studies with a larger cohort of dogs focusing on IE in comparison to healthy dogs are indicated
Summary
Chemokines such as MIP-3β/CCL19 are important factors in the mechanism of cell migration and pathogenesis of central nervous system (CNS) inflammatory reactions. In spinal cord injury involving intervertebral disc herniation, a local inflammatory reaction has been documented [30] and the macrophage count within the CSF is thought to be positively associated with the degree of spinal cord damage [31]. With this investigation, we seek to understand the role of CCL19 in the aforementioned CNS diseases in dogs and establish whether this chemokine is generally associated with CNS inflammation or specific to certain diseases
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