Elevated Interleukin-31 Levels in Serum, but Not CSF of Dogs with Steroid-Responsive Meningitis-Arteritis Suggest an Involvement in Its Pathogenesis

SIMPLE SUMMARY: Steroid-responsive meningitis-arteritis (SRMA) is a common immune-mediated inflammatory disease of young-adult dogs with predominantly neck pain and fever. The exact pathomechanism of this disease remains unclear. Interleukin-31 is a cytokine that has been shown to be elevated among other things in dogs with atopic dermatitis and dogs with a typical phenotype of inflammation (Th2-mediated) in previous studies. This phenotype of inflammation is typical for SRMA. Therefore, we suggested that interleukin-31 might be involved in the pathomechanism of SRMA. Within the study, interleukin-31 levels were measured in serum and cerebrospinal fluid samples of dogs affected by SRMA in comparison to dogs with atopic dermatitis (positive control), healthy dogs (negative control) and dogs with immune-mediated or infectious meningoencephalitis. The serum interleukin-31 levels of dogs with SRMA were markedly higher than in healthy control dogs. Especially dogs with SRMA without any pre-treatment showed markedly higher interleukin-31 levels. The cerebrospinal fluid interleukin-31 levels revealed no differences between the groups. Based on this study, an involvement of interleukin-31 in the pathogenesis of SRMA can be assumed, but further clarification is necessary with prospective studies. We suggest that our study might help to clarify further parts of the pathogenesis of SRMA. ABSTRACT: Steroid-responsive meningitis-arteritis (SRMA) is a predominantly Th-2 immune-mediated disease, but the exact pathomechanism remains unclear. Interleukin-31 (IL-31) is predominantly produced by T cells with a Th-2 phenotype during proinflammatory conditions. We hypothesize that IL-31 might be involved in the pathogenesis of SRMA. IL-31 was measured in archived samples (49 serum and 52 CSF samples) of dogs with SRMA, meningoencephalitis of unknown origin (MUO), infectious meningoencephalitis, and atopic dermatitis, and of healthy control dogs using a competitive canine IL-31 ELISA. The mean serum IL-31 level in dogs with SRMA (n = 18) was mildly higher compared to dogs with atopic dermatitis (n = 3, p = 0.8135) and MUO (n = 15, p = 0.7618) and markedly higher than in healthy controls (n = 10, p = 0.1327) and dogs with infectious meningoencephalitis (n = 3, no statistics). Dogs with SRMA in the acute stage of the disease and without any pre-treatment had the highest IL-31 levels. The mean CSF IL-31 value for dogs with SRMA (n = 23) was quite similar to that for healthy controls (n = 8, p = 0.4454) and did not differ markedly from dogs with MUO (n = 19, p = 0.8724) and infectious meningoencephalitis. Based on this study, an involvement of IL-31 in the pathogenesis of the systemic Th-2 immune-mediated immune response in SRMA can be assumed as a further component leading to an aberrant immune reaction.