Send to

Choose Destination
Brain. 2003 Aug;126(Pt 8):1873-82. Epub 2003 Jun 23.

Lack of IL-6 augments inflammatory response but decreases vascular permeability in bacterial meningitis.

Author information

Department of Neurology, Klinikum Grosshadern, Ludwig-Maximilians-University of Munich, Marchioninistrasse 15, 81377 Munich, Germany.


Interleukin (IL)-6 is a multifunctional cytokine with diverse actions and has been implicated in the pathophysiology of many neurological and inflammatory disorders. In this study, we investigated the role of IL-6 in pneumococcal meningitis. Cerebral infection in wild-type (WT) mice caused an increase in vascular permeability and intracranial pressure (ICP), which were significantly reduced in IL-6-/- mice. In contrast, meningitis in IL-6-/- mice was associated with a significant increase in CSF white blood cell count compared with infected WT mice, indicating an enhanced inflammatory response. Analysis of mRNA expression in the brain showed an increase in tumour necrosis factor (TNF)-alpha, IL-1beta, and macrophage inflammatory protein 2 (MIP-2) levels, but decreased expression of granulocyte-macrophage colony-stimulating factor in infected IL-6-/- mice compared with infected WT controls. Similar results were obtained when rats challenged with pneumococci were systemically treated with neutralizing anti-IL-6 antibodies, resulting in an increased pleocytosis but at the same time a reduction of vascular permeability, brain oedema formation, and ICP, which was not accompanied by a downregulation of matrix metalloproteinases. Our data indicate that IL-6 plays an important anti-inflammatory role in bacterial meningitis by reducing leukocyte infiltration but contributes to the rise in intracranial pressure by increasing blood-brain barrier (BBB) permeability. These findings suggest that the migration of leukocytes across the BBB and the increase in vascular permeability are two independent processes during bacterial meningitis.

[Indexed for MEDLINE]
Free full text

Supplemental Content

Full text links

Icon for Silverchair Information Systems Icon for Zurich Open Access Repository and Archive
Loading ...
Support Center