Sequential analysis of biomarkers in cerebrospinal fluid and serum during invasive meningococcal disease

Abstract

The aim of the present study was to determine the profile of different inflammatory molecules in serum and cerebrospinal fluid (CSF) during invasive meningococcal disease (IMD). Their relationship with IMD severity was also assessed. A cohort of 12 patients with IMD was investigated. Paired serum and CSF samples were obtained at the time of diagnostic and follow-up lumbar puncture and were examined using Luminex® analysis. IMD severity correlated with serum interleukin-6 (IL-6) and interleukin-1 receptor antagonist (IL-1ra) on admission. Furthermore, the CSF levels of IL-1β, IL-1ra, IL-6, IL-8, macrophage inflammatory protein-1β (MIP-1β), and monocyte chemoattractant protein-1 (MCP-1) were significantly higher than their respective serum levels. The strongest correlations were found between serum concentrations of IL-1β and IL-1ra, IL-6, IL-8, and MIP-1β, whereas the strongest correlations in CSF were found between endotoxin and IL-8, IL-17, MIP-1β, and MCP-1. As was expected, the concentrations of inflammatory molecules in both serum and CSF significantly decreased after antibiotic treatment. With regard to kinetics, a severe course of IMD correlated positively with rapid declines of CSF IL-6 and cortisol levels. Sequential multiple analyses revealed patterns of inflammatory responses that were associated with the severity of IMD, as well as with the compartmentalization and kinetics of the immune reaction.