Cerebrospinal fluid inflammatory markers in patients with Listeria monocytogenes meningitis

BACKGROUND: Listeria monocytogenes meningitis is the third most common cause of bacterial meningitis and is associated with high rates of mortality and unfavorable outcome. METHODS: We analyzed 101 cytokines, chemokines and complement factors in CSF of adult patients with Listeria meningitis included in a prospective cohort study and compared these biomarkers between Listeria meningitis patients and negative controls, and between Listeria meningitis patients with a favorable and an unfavorable outcome. RESULTS: CSF was available from 26 of 62 (42%) Listeria meningitis patients and 19 negative controls. Fifteen (58%) Listeria meningitis patients had an unfavorable outcome. In Listeria meningitis CSF levels of 51 biomarkers were significantly elevated compared to negative controls after Bonferroni correction. The 11 most significantly elevated (P < .01) biomarkers of unfavorable outcome in Listeria meningitis were markers of T-cell activation (sIL-2Rα, sCD40L and IL-1), interferon-related (IFN-α2, IL-18, CX3CL1, CCL20), markers of complement activation (C3a), and endothelial growth factor related (VEGF, CXCL7). CONCLUSIONS: Our data suggest that T-cell activation, complement activation, interferon- and endothelial growth factor production are important in the immune response to Listeria meningitis, and thereby influence outcome. GENERAL SIGNIFICANCE: Our study provides target pathways for further studies in the pathophysiology of Listeria meningitis.