Cerebrospinal fluid type I interferon and cytokine profiles in enteroviral meningitis according to the presence or absence of pleocytosis

Abstract

Enteroviral meningitis is typically diagnosed as the presence of pleocytosis and of viral RNA in cerebrospinal fluid. However, it was recently reported that more than 50% of infants with enteroviral meningitis diagnosed by polymerase chain reaction had no cerebrospinal fluid pleocytosis. This study investigated type I interferon (IFN) and cytokine profiles in the cerebrospinal fluid based on the presence or absence of cerebrospinal fluid pleocytosis in children with enteroviral meningitis. We included 51 enteroviral meningitis patients showing cerebrospinal fluid pleocytosis (pleocytosis group), 31 enteroviral meningitis patients without cerebrospinal fluid pleocytosis (non-pleocytosis group), and 52 controls (control group) and compared cerebrospinal fluid interleukin 6 (IL-6), IL-8, chemokine (C-X-C motif) ligand 10 (CXCL-10), IFN-α, and IFN-β levels. A significant difference was observed in IL-6, IL-8, and CXCL-10 levels across the three groups, with highest values in the pleocytosis patients, followed by those in the non-pleocytosis and control subjects. IFN-α level was higher in the pleocytosis group than in the non-pleocytosis and control groups. Meanwhile, the IFN-β level was higher in the pleocytosis and non-pleocytosis groups than in the control group (34.54 [31.23-38.59] pg/mL vs. 33.21 [31.23-35.21] pg/mL vs. 0.00 [0.00-0.00]pg/mL, respectively; P<0.001). Furthermore, cerebrospinal fluid IFN-β was detected in all patients with enteroviral meningitis, except one (98.8%) regardless of pleocytosis, whereas it was detected in only two (3.8%) control subjects (P<0.001). The cerebrospinal fluid cytokine profiles remarkably differed based on the presence or absence of cerebrospinal fluid pleocytosis. Further investigations are required to determine whether cerebrospinal fluid IFN-β could be used as a surrogate marker of viral meningitis instead of cerebrospinal fluid pleocytosis.