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

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-β(1)), 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- β(1). 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-β(1) 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-β(1) between the different groups. In untreated SRMA patients, a positive correlation (r(Spear) = 0.3549; P = 0.0337) between concentrations of TGF-β(1) and IgA concentration was found in CSF, while concentrations of IL-6 and VEGF in CSF positively correlated with the degree of pleocytosis (r(Spear) = 0.8323; P < 0.0001 and r(Spear) = 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-β(1) is considered to be involved in the excessive IgA production, while IL-6 in the pleocytosis. The combined intrathecal increase of TGF-β(1) 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.