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Open Access Highly Accessed Research article

Interleukin-6, vascular endothelial growth factor and transforming growth factor beta 1 in canine steroid responsive meningitis-arteritis

Arianna Maiolini12*, Meike Otten3, Marion Hewicker-Trautwein4, Regina Carlson1 and Andrea Tipold12

Author Affiliations

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

2 Center for Systems Neuroscience, Hannover, Germany

3 Veterinary Practice Peter Gravert and Dr. Volker Otten, Gettorf, Germany

4 Department of Pathology, University of Veterinary Medicine, Hannover, Germany

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BMC Veterinary Research 2013, 9:23  doi:10.1186/1746-6148-9-23

Published: 4 February 2013

Abstract

Background

Steroid Responsive Meningitis-Arteritis (SRMA) is a common cause of inflammation of the canine central nervous system (CNS). To investigate if transforming growth factor beta 1 (TGF-β1), interleukin-6 (IL-6) and vascular endothelial growth factor (VEGF) are involved in the production of excessive immunoglobulin A (IgA), the induction of acute phase proteins and in the development of a systemic necrotizing vasculitis, characteristic of SRMA, these three signalling proteins were evaluated.

Results

Cerebrospinal fluid (CSF) and serum samples of dogs during the acute phase of SRMA (SRMA) were tested for IL-6, VEGF and TGF- β1. Results were compared to those of dogs affected with SRMA during treatment (SRMA Th) and during relapse (SRMA R), to dogs with other meningoencephalomyelitides (ME), with miscellaneous non-inflammatory diseases of the CNS (CNS-Mix), with idiopathic epilepsy (IE), with systemic inflammatory diseases (Syst. Infl.) and with healthy dogs (Healthy). Concentrations of IL-6 and VEGF in CSF were significantly elevated in the SRMA group compared to the other disease categories (p < 0.05). The CSF concentrations of TGF-β1 were increased in SRMA group, but statistically significant differences were found only in comparison with Healthy and CNS-Mix groups. No differences were detected in the serum concentrations of TGF-β1 between the different groups. In untreated SRMA patients, a positive correlation (rSpear = 0.3549; P = 0.0337) between concentrations of TGF-β1 and IgA concentration was found in CSF, while concentrations of IL-6 and VEGF in CSF positively correlated with the degree of pleocytosis (rSpear = 0.8323; P < 0.0001 and rSpear = 0.5711; P = 0.0166, respectively).

Conclusions

Our results suggest that these three signalling proteins are biomarkers of disease activity in SRMA. VEGF might play an important role in the development of a systemic arteritis. TGF-β1 is considered to be involved in the excessive IgA production, while IL-6 in the pleocytosis. The combined intrathecal increase of TGF-β1 and IL-6 detected in SRMA could possibly force CD4 progenitors to differentiate towards the newly described Th17 lymphocyte subset and enhance the autoimmune response.

Keywords:
Steroid responsive meningitis-arteritis (SRMA); Interleukin-6 (IL-6); Transforming growth factor beta 1 (TGF-β1); Vascular endothelial growth factor (VEGF); Cerebrospinal fluid (CSF); Dog; Central nervous system (CNS)