Interleukin-1β and interleukin-1 receptor antagonist appear in grey matter additionally to white matter lesions during experimental multiple sclerosis.

<h4>Background</h4>Multiple sclerosis (MS) has been mainly attributed to white matter (WM) pathology. However, recent evidence indicated the presence of grey matter (GM) lesions. One of the principal mediators of inflammatory processes is interleukin-1β (IL-1β), which is known to play a...

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Autores principales:	Marloes Prins, Charlotta Eriksson, Anne Wierinckx, John G J M Bol, Rob Binnekade, Fred J H Tilders, Anne-Marie Van Dam
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2013
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/fc67a8807be442f1acb32145dcd6bf13
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spelling	oai:doaj.org-article:fc67a8807be442f1acb32145dcd6bf132021-11-18T08:40:33ZInterleukin-1β and interleukin-1 receptor antagonist appear in grey matter additionally to white matter lesions during experimental multiple sclerosis.1932-620310.1371/journal.pone.0083835https://doaj.org/article/fc67a8807be442f1acb32145dcd6bf132013-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/24376764/?tool=EBIhttps://doaj.org/toc/1932-6203<h4>Background</h4>Multiple sclerosis (MS) has been mainly attributed to white matter (WM) pathology. However, recent evidence indicated the presence of grey matter (GM) lesions. One of the principal mediators of inflammatory processes is interleukin-1β (IL-1β), which is known to play a role in MS pathogenesis. It is unknown whether IL-1β is solely present in WM or also in GM lesions. Using an experimental MS model, we questioned whether IL-1β and the IL-1 receptor antagonist (IL-1ra) are present in GM in addition to affected WM regions.<h4>Methods</h4>The expression of IL-1β and IL-1ra in chronic-relapsing EAE (cr-EAE) rats was examined using in situ hybridization, immunohistochemistry and real-time PCR. Rats were sacrificed at the peak of the first disease phase, the trough of the remission phase, and at the peak of the relapse. Histopathological characteristics of CNS lesions were studied using immunohistochemistry for PLP, CD68 and CD3 and Oil-Red O histochemistry.<h4>Results</h4>IL-1β and IL-ra expression appears to a similar extent in affected GM and WM regions in the brain and spinal cord of cr-EAE rats, particularly in perivascular and periventricular locations. IL-1β and IL-1ra expression was dedicated to macrophages and/or activated microglial cells, at sites of starting demyelination. The time-dependent expression of IL-1β and IL-1ra revealed that within the spinal cord IL-1β and IL-1ra mRNA remained present throughout the disease, whereas in the brain their expression disappeared during the relapse.<h4>Conclusions</h4>The appearance of IL-1β expressing cells in GM within the CNS during cr-EAE may explain the occurrence of several clinical deficits present in EAE and MS which cannot be attributed solely to the presence of IL-1β in WM. Endogenously produced IL-1ra seems not capable to counteract IL-1β-induced effects. We put forward that IL-1β may behold promise as a target to address GM, in addition to WM, related pathology in MS.Marloes PrinsCharlotta ErikssonAnne WierinckxJohn G J M BolRob BinnekadeFred J H TildersAnne-Marie Van DamPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 8, Iss 12, p e83835 (2013)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Marloes Prins Charlotta Eriksson Anne Wierinckx John G J M Bol Rob Binnekade Fred J H Tilders Anne-Marie Van Dam Interleukin-1β and interleukin-1 receptor antagonist appear in grey matter additionally to white matter lesions during experimental multiple sclerosis.
description	<h4>Background</h4>Multiple sclerosis (MS) has been mainly attributed to white matter (WM) pathology. However, recent evidence indicated the presence of grey matter (GM) lesions. One of the principal mediators of inflammatory processes is interleukin-1β (IL-1β), which is known to play a role in MS pathogenesis. It is unknown whether IL-1β is solely present in WM or also in GM lesions. Using an experimental MS model, we questioned whether IL-1β and the IL-1 receptor antagonist (IL-1ra) are present in GM in addition to affected WM regions.<h4>Methods</h4>The expression of IL-1β and IL-1ra in chronic-relapsing EAE (cr-EAE) rats was examined using in situ hybridization, immunohistochemistry and real-time PCR. Rats were sacrificed at the peak of the first disease phase, the trough of the remission phase, and at the peak of the relapse. Histopathological characteristics of CNS lesions were studied using immunohistochemistry for PLP, CD68 and CD3 and Oil-Red O histochemistry.<h4>Results</h4>IL-1β and IL-ra expression appears to a similar extent in affected GM and WM regions in the brain and spinal cord of cr-EAE rats, particularly in perivascular and periventricular locations. IL-1β and IL-1ra expression was dedicated to macrophages and/or activated microglial cells, at sites of starting demyelination. The time-dependent expression of IL-1β and IL-1ra revealed that within the spinal cord IL-1β and IL-1ra mRNA remained present throughout the disease, whereas in the brain their expression disappeared during the relapse.<h4>Conclusions</h4>The appearance of IL-1β expressing cells in GM within the CNS during cr-EAE may explain the occurrence of several clinical deficits present in EAE and MS which cannot be attributed solely to the presence of IL-1β in WM. Endogenously produced IL-1ra seems not capable to counteract IL-1β-induced effects. We put forward that IL-1β may behold promise as a target to address GM, in addition to WM, related pathology in MS.
format	article
author	Marloes Prins Charlotta Eriksson Anne Wierinckx John G J M Bol Rob Binnekade Fred J H Tilders Anne-Marie Van Dam
author_facet	Marloes Prins Charlotta Eriksson Anne Wierinckx John G J M Bol Rob Binnekade Fred J H Tilders Anne-Marie Van Dam
author_sort	Marloes Prins
title	Interleukin-1β and interleukin-1 receptor antagonist appear in grey matter additionally to white matter lesions during experimental multiple sclerosis.
title_short	Interleukin-1β and interleukin-1 receptor antagonist appear in grey matter additionally to white matter lesions during experimental multiple sclerosis.
title_full	Interleukin-1β and interleukin-1 receptor antagonist appear in grey matter additionally to white matter lesions during experimental multiple sclerosis.
title_fullStr	Interleukin-1β and interleukin-1 receptor antagonist appear in grey matter additionally to white matter lesions during experimental multiple sclerosis.
title_full_unstemmed	Interleukin-1β and interleukin-1 receptor antagonist appear in grey matter additionally to white matter lesions during experimental multiple sclerosis.
title_sort	interleukin-1β and interleukin-1 receptor antagonist appear in grey matter additionally to white matter lesions during experimental multiple sclerosis.
publisher	Public Library of Science (PLoS)
publishDate	2013
url	https://doaj.org/article/fc67a8807be442f1acb32145dcd6bf13
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Interleukin-1β and interleukin-1 receptor antagonist appear in grey matter additionally to white matter lesions during experimental multiple sclerosis.

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