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. 2025 May 21;20(5):e0324153.
doi: 10.1371/journal.pone.0324153. eCollection 2025.

Pneumococcal meningitis and endotoxemia: A cross-sectional clinical study

Sylvie Nguyen  1 , Jeanne Godon  2 , Jean-Paul Pais de Barros  3 , David Masson  1 , Lionel Piroth  2   4 , Mathieu Blot  1   2   4 ; Meningotoxemia collaboration group
Affiliations

Pneumococcal meningitis and endotoxemia: A cross-sectional clinical study

Sylvie Nguyen et al. PLoS One. .

Abstract

Introduction: Lipopolysaccharide (LPS) is a major virulence factor during both meningococcal and Haemophilus influenzae meningitis. Pneumococcus does not produce LPS but could be responsible for bacterial digestive translocation as a consequence of sepsis. We addressed this question in the context of pneumococcal meningitis.

Methods: A cross-sectional study on 24 patients with pneumococcal meningitis (20 (83%) admitted in intensive care unit, 4 (17%) with septic shock) and 34 prospectively-enrolled healthy volunteers. Interleukin 6 and C-reactive proteins plasma concentrations were measured as markers of systemic inflammation. Endotoxemia was measured using mass spectrometry (LC-MS/MS) for detection of molecules bound to the lipid A, namely 3-OH fatty acids.

Results: Meningitis patients had significantly higher levels of plasma C-reactive protein (237 (74-373) vs. 2 (2-2) mg/l, p < 0.001 and interleukin 6 (43 (13-128) vs. 4.6 (4.6-16.6) pg/ml; p < 0.001) than healthy volunteers. However, we observed no significant difference in plasma lipopolysaccharide concentrations between patients and healthy volunteers (674 (554-896) vs. 668 (623-777) pmol/ml; p = 0.546).

Conclusions: Our results suggest that LPS is not a key determinant of the excessive inflammation associated with severe forms of pneumococcal meningitis.

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Conflict of interest statement

All the authors have no conflicts of interest to report.

Figures

Fig 1
Fig 1. Plasma inflammatory response, LPS concentrations, and marker of gut barrier integrity in 24 patients prospectively included with a pneumococcal meningitis and 34 healthy volunteers (Meningotoxemia study, 2023). Plasma C-reactive protein (A), IL-6 (B), LPS (C) and i-FABP (D) concentrations were measured. LPS concentrations were measured using a mass spectrometry (LC-MS/MS) patented method for detection of 3-OH fatty acids (C10, C12, C14, C16 and C18), which are molecules bound to the lipid A motif of LPS.Abbreviations: CRP: C-reactive protein, HV: healthy volunteers, i-FABP: intestinal-Fatty-acid-binding protein, IL-6: interleukin 6, LC-MS/MS: liquid chromatography coupled to tandem mass spectrometry, LPS: lipopolysaccharide.
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