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.

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)-1beta and TNF-alpha) 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-alpha ( 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 (r(2)=0.7, p<0.001) and E-selectin (r(2)=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.