Eosinophil recruitment and activation in the central nervous system of patients with subarachnoid neurocysticercosis.

Abstract

Background and objectives: Subarachnoid neurocysticercosis (SANCC) is the most severe manifestation of neurocysticercosis. Most complications (communicating hydrocephalus, ischemic stroke, aneurysm, and subarachnoid hemorrhage) are due to inflammation localized to the central nervous system (CNS). The role of eosinophils in the inflammation associated with SANCC has not been previously studied.

Methods: Cryopreserved CSF collected as part of a clinical trial for neurocysticercosis (NCC) were assessed for analytes associated with eosinophil activation and recruitment using multiplex bead assays in both subjects with SANCC (n = 28) and in NCC-negative controls (n = 26). The SANCC patients underwent chart review for extraction of clinical variables as well as grouping by disease severity to identify analytes that may be associated with the development of more severe symptoms of SANCC.

Results: Eosinophil granule proteins (EGPs - ECP, EDN, and EPO), markers of eosinophil activation, were elevated in the CSF of SANCC patients compared to controls. Moreover, the eosinophil-associated cytokines/chemokines IL-5, IL-13, IL-18, CCL24/eotaxin-2, and CCL26/eotaxin-3 were also significantly elevated in the CSF of SANCC patients compared to controls. In those for whom there were paired specimens (n = 13) from baseline and following cure, there was a significant reduction in these cytokines/chemokines (except CCL26/eotaxin-3). The percentage of CSF white blood cells that were eosinophils was positively correlated with EDN, EPO, IL-5, IL-13, CCL24, CCL26, CCL8, CCL13, and CCL5/RANTES, as well as the time it took to achieve biomarker cure. When SANCC patients were subdivided between those with severe disease and those with non-severe disease, the levels of eosinophil cationic protein (ECP), the CCR3 ligands (CCL7 and CCL5), CCL4, IL-18, and IL-1RA discriminated clearly between these 2 groups.  DISCUSSION: These data provide evidence for eosinophil recruitment and activation in the subarachnoid space in patients with SANCC, as well as for a potential role of eosinophils in driving inflammation-associated complications.