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Increased diffusion of soluble adhesion molecules in meningitis, severe sepsis and systemic inflammatory response without neurological infection is associated with intrathecal shedding in cases of meningitis

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Abstract

Objective

Sepsis and systemic inflammatory response syndrome (SIRS) result in the release in plasma of inflammatory cytokines and soluble forms of adhesion molecules in relation to endothelial activation. This study was designed to compare cerebrospinal fluid (CSF) concentrations of adhesion molecules in meningitis and SIRS without neurological infection and to evaluate in meningitis whether they originate from passive diffusion through damaged blood–CSF barrier or from local production.

Design

Prospective observational study.

Setting

University hospital medical intensive care unit.

Patients

Nineteen patients with meningitis and 41 patients with sepsis or SIRS without cerebrospinal infection consecutively admitted to the critical care unit over an 18-month period.

Interventions

Soluble forms of adhesion molecules (ICAM-1, VCAM-1, E-selectin) and cytokines (interleukin (IL)-1β and TNF−α) were measured in paired CSF and blood samples.

Results

Serum concentrations of soluble adhesion molecules and cytokines were increased in the two groups, without significant differences. The CSF concentrations were elevated in both cases, whereas patients with meningitis demonstrated significantly higher CSF concentrations of soluble ICAM-1, VCAM-1, E-selectin, and TNF-α (p<0.001), with higher corresponding CSF/serum ratios. Correlations between CSF and serum concentrations were found only in meningitis. These correlations were strong for soluble ICAM-1 (r2=0.7, p<0.001) and E-selectin (r2=0.9, p<0.001), but weaker for VCAM-1. VCAM-1 CSF/serum ratios were increased, in comparison with ICAM-1 and E-selectin CSF/serum ratios, despite similar molecular weights. Serum and CSF levels of cytokines and adhesion molecules were not predictive of death for the whole population, except concentrations of ICAM-1 significantly increased in non-surviving patients (p<0.05).

Conclusions

The CSF soluble adhesion molecules are increased in sepsis, SIRS and meningitis. In meningitis, the correlation between CSF and serum concentrations of adhesion molecules and the presence of a discrepancy of CSF/serum ratios for molecules of the same molecular weight may suggest intrathecal shedding in addition to diffusion through blood–CSF barrier.

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Author notes

  1. Bruno Mégarbane

    Present address: Réanimation Médicale et Toxicologique, Hôpital Lariboisière, 2 rue Ambroise Paré, 75010, Paris, France

Authors and Affiliations

  1. Department of Medical Intensive Care Unit and Medical Emergency, AP-HP Antoine Béclère Hospital, Clamart, France

    Bruno Mégarbane, Philippe Marchal, Frédéric Jacobs, Isabelle Chary & François G. Brivet

  2. Laboratory of Immuno-Hematology, Antoine Béclère Hospital, Clamart, France

    Anne Marfaing-Koka & Olivier Belliard

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  1. Bruno Mégarbane
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  2. Philippe Marchal
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Correspondence to Bruno Mégarbane.

Additional information

This work was presented in part, at the 27th Congress of The Société de Réanimation de Langue Française, Paris, France, January 1999, and at the 27th Congress of The European Society of Intensive Care Medicine, Berlin, Germany, October 1999.

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Mégarbane, B., Marchal, P., Marfaing-Koka, A. et al. Increased diffusion of soluble adhesion molecules in meningitis, severe sepsis and systemic inflammatory response without neurological infection is associated with intrathecal shedding in cases of meningitis. Intensive Care Med 30, 867–874 (2004). https://doi.org/10.1007/s00134-004-2253-1

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