Cerebrospinal Fluid Cytokine and Chemokine Analysis in Dogs With Meningoencephalitis of Unknown Origin or Idiopathic Epilepsy

Abstract

Background: Current diagnosis of brain disease in dogs is dependent on imaging and cerebrospinal fluid (CSF) analysis, including total nucleated cell counts and albumin concentrations. Hypothesis/Objectives: To determine whether multiplex cytokine/chemokine (Ct/Cm) analysis can differentiate among dogs with meningoencephalitis of unknown origin (MUE), idiopathic epilepsy (IE), and brain neoplasia. Animals: Client owned dogs diagnosed with brain disease with MRI and CSF diagnostics. Groups included 18 dogs with a diagnosis of MUE, 21 dogs with IE, and 7 dogs with brain tumors. Methods: A retrospective observational study; a multiplex immunoassay was utilized to measure CSF concentrations for the following: Interleukin (IL)-2, IL-6, IL-7, IL-8, IL-10, IL-15, and IL-18, granulocyte macrophage colony-stimulating factor (GM-CSF), interferon gamma (IFN-γ), keratinocyte chemoattractant (KC)-like protein, IFN-γ-inducible protein-10 (IP-10), monocyte chemotactic protein 1 (MCP-1), and tumor necrosis factor alpha (TNF-α). Results: Several Ct/Cm were detected only in MUE cases: GM-CSF (9/18), IFN-γ (13/18), IL-2 (8/18), IL-15 (4/18), and TNF-α (11/18). Other Ct/Cm concentrations were significantly higher in MUE cases (IL-8: median 101 pg/mL, range 144, p = 0.019; IL-18: median 3 pg/mL, range 0.52, p < 0.001; MCP-1: median 814 pg/mL, range 1319, p = 0.004; and IL-6: median 5 pg/mL, range 16, p < 0.001) compared to epilepsy and neoplasia. Conclusions and Clinical Importance: IFN-γ, TNF-α, GM-CSF, IL-2, and IL-15 might be specific markers of MUE in canine CSF and could be potentially useful biomarkers in the diagnosis of MUE.