title: Interleukin-1β and interleukin-1 receptor antagonist appear in grey matter additionally to white matter lesions during experimental multiple sclerosis.
abstract: BACKGROUND
  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.
  
  
  METHODS
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: VU University Medical Center, Neuroscience Campus Amsterdam, Dept. Anatomy and Neurosciences, Amsterdam, The Netherlands.
authors.forename: Marloes
authors.initials: M
authors.lastname: Prins
authors.affiliation: VU University Medical Center, Neuroscience Campus Amsterdam, Dept. Anatomy and Neurosciences, Amsterdam, The Netherlands.
authors.forename: Charlotta
authors.initials: C
authors.lastname: Eriksson
authors.affiliation: VU University Medical Center, Neuroscience Campus Amsterdam, Dept. Anatomy and Neurosciences, Amsterdam, The Netherlands ; UNIV UMR1052, Centre de Recherche en Cancérologie de Lyon, Lyon, France.
authors.forename: Anne
authors.initials: A
authors.lastname: Wierinckx
authors.affiliation: VU University Medical Center, Neuroscience Campus Amsterdam, Dept. Anatomy and Neurosciences, Amsterdam, The Netherlands.
authors.forename: John G J M
authors.initials: JG
authors.lastname: Bol
authors.affiliation: VU University Medical Center, Neuroscience Campus Amsterdam, Dept. Anatomy and Neurosciences, Amsterdam, The Netherlands.
authors.forename: Rob
authors.initials: R
authors.lastname: Binnekade
authors.affiliation: VU University Medical Center, Neuroscience Campus Amsterdam, Dept. Anatomy and Neurosciences, Amsterdam, The Netherlands.
authors.forename: Fred J H
authors.initials: FJ
authors.lastname: Tilders
authors.affiliation: VU University Medical Center, Neuroscience Campus Amsterdam, Dept. Anatomy and Neurosciences, Amsterdam, The Netherlands.
authors.forename: Anne-Marie
authors.initials: AM
authors.lastname: Van Dam
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D005786:Gene Expression Regulation; D066128:Gray Matter / Q000378:metabolism* / Q000473:pathology; D053590:Interleukin 1 Receptor Antagonist Protein / Q000235:genetics* / Q000378:metabolism*; D053583:Interleukin-1beta / Q000235:genetics* / Q000378:metabolism*; D008297:Male; D009103:Multiple Sclerosis / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D021381:Protein Transport; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D012008:Recurrence; D066127:White Matter / Q000378:metabolism* / Q000473:pathology
chemical_list: D053590:Interleukin 1 Receptor Antagonist Protein; D053583:Interleukin-1beta; D012333:RNA, Messenger