Cerebrospinal fluid levels of soluble CD14 in inflammatory and non-inflammatory diseases of the CNS: upregulation during bacterial infections and viral meningitis

The CD14 antigen, an important cell surface molecule of monocytic cells, is involved in cellular activation: it binds lipopolysaccharide and other cel lular lipid structures. Brain macrophages play a pivotal role during inflam matory reactions of the CNS parenchyma, ventricles and meninges. A soluble form of CD14 (sCD14) was measured in paired cerebrospinal fluid (CSF) and s erum samples from 91 patients with different neurological diseases. Mean le vels of circulating sCD14 in CSF in a control group of 22 patients with neu rologic complaints but no neurological deficit on clinical examination were 0.19 +/- 0.06 (mean +/- SD) mg/l. The CSF/blood ratios of sCD14 was 49 +/- 16 X 10(-3), while those of albumin were 4.4 +/- 1.4 X 10(-3). These extre mely high CSF/blood ratios of the sCD14 molecule compared to albumin indica te a local cerebral production. No significant changes in CSF sCD14 levels were found in patients with non-inflammatory neurological diseases (NID). I n contrast, CSF sCD14 levels were markedly elevated during acute meningitis , but there was no direct correlation between sCD14 and monocyte count in t he CSF. Thus, sCD14 could not originate in the CSF compartment from monocyt es alone. The highest values for sCD14 were found in CSF during infections with various pathogens such as Staphylococcus aureus or Listeria monocytoge nes. While sCD14 serum levels dramatically increased during acute bacterial meningitis, sCD14 ratios did not correlate with albumin ratios during the course of disease. Therefore, increased CSF sCD14 may originate from cerebr al production by activated or infiltrated macrophages rather than passive d iffusion from the blood, while elevated sCD14 serum levels resulted from en hanced local production. Increased CSF and serum sCD14 values were also obs erved in meningitis caused by viral infection. As in bacterial meningitis, sCD14 in CSF specimens did not correlate with the function of the blood/CSF barrier. Repeated lumbar punctures revealed a normalization of CSF sCD14 l evels during clinical recovery. These results provide the first evidence fo r local production of sCD14 within the CNS. Our findings further indicate t hat sCD14 in CSF is a reliable marker for activation of macrophages within the CNS during inflammatory processes. (C) 1999 Elsevier Science B.V. All r ights reserved.