IL-6 transsignalling modulates the early effector phase of EAE and targets the blood-brain barrier

Linker, Ralf A; Lühder, Fred; Kallen, Karl-Josef; Lee, De-Hyung; Engelhardt, Britta; Rose-John, Stefan; Gold, Ralf (2008). IL-6 transsignalling modulates the early effector phase of EAE and targets the blood-brain barrier. Journal of neuroimmunology, 205(1-2), pp. 64-72. Amsterdam: Elsevier 10.1016/j.jneuroim.2008.09.007

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Interleukin-6 (IL-6) plays a crucial role in the pathogenesis of experimental autoimmune encephalomyelitis (EAE). It exerts its cellular effects by a membrane-bound IL-6 receptor (IL-6R), or, alternatively, by forming a complex with the soluble IL-6R (sIL-6R), a process named IL-6 transsignalling. Here we investigate the role of IL-6 transsignalling in myelin basic protein (MBP)-induced EAE in the Lewis rat. In vivo blockade of IL-6 transsignalling by the injection of a specifically designed gp130-Fc fusion protein significantly delayed the onset of adoptively transferred EAE in comparison to control rats injected with PBS or isotype IgG. Histological evaluation on day 3 after immunization revealed reduced numbers of T cells and macrophages in the lumbar spinal cord of gp130-Fc treated rats. At the same time, blockade of IL-6 transsignalling resulted in a reduced expression of vascular cell adhesion molecule-1 on spinal cord microvessels while experiments in cell culture failed to show a direct effect on the regulation of endothelial adhesion molecules. In experiments including active EAE and T cell culture, inhibition of IL-6 transsignalling mildly increased T cell proliferation, but did not change severity of active MBP-EAE or regulate Th1/Th17 responses. We conclude that IL-6 transsignalling may play a role in autoimmune inflammation of the CNS mainly by regulating early expression of adhesion molecules, possibly via cellular networks at the blood-brain barrier.

Item Type:	Journal Article (Original Article)
Division/Institute:	04 Faculty of Medicine > Pre-clinic Human Medicine > Theodor Kocher Institute
UniBE Contributor:	Engelhardt, Britta
ISSN:	0165-5728
ISBN:	18950871
Publisher:	Elsevier
Language:	English
Submitter:	Factscience Import
Date Deposited:	04 Oct 2013 15:05
Last Modified:	05 Dec 2022 14:20
Publisher DOI:	10.1016/j.jneuroim.2008.09.007
PubMed ID:	18950871
Web of Science ID:	000261902200011
URI:	https://boris.unibe.ch/id/eprint/28190 (FactScience: 118484)