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

Abstract

Background: 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.

Methods: 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.

Results: 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).

Conclusion: 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.

Keywords: cerebrospinal fluid; cytokines; enteroviral meningitis; interferon-beta; pleocytosis.