Expression of IL-1β in rhesus EAE and MS lesions is mainly induced in the CNS itself.
Interleukin (IL)-1β is a pro-inflammatory cytokine that plays a role in the pathogenesis of multiple sclerosis (MS) and experimental autoimmune encephalomyelitis (EAE), the animal model for MS. Yet, detailed studies on IL-1β expression in different stages of MS lesion development and a comparison of IL-1β expression in MS and EAE are lacking.



Here, we performed an extensive characterization of IL-1β expression in brain tissue of MS patients, which included different MS lesion types, and in brain tissue of rhesus macaques with EAE.



In rhesus EAE brain tissue, we observed prominent IL-1β staining in MHC class II(+) cells within perivascular infiltrates and at the edges of large demyelinating lesions. Surprisingly, staining was localized to resident microglia or differentiated macrophages rather than to infiltrating monocytes, suggesting that IL-1β expression is induced within the central nervous system (CNS). By contrast, IL-1β staining in MS brain tissue was much less pronounced. Staining was found in the parenchyma of active and chronic active MS lesions and in nodules of MHC class II(+) microglia in otherwise normal appearing white matter. IL-1β expression was detected in a minority of the nodules only, which could not be distinguished by the expression of pro- and anti-inflammatory markers. These nodules were exclusively found in MS, and it remains to be determined whether IL-1β(+) nodules are destined to progress into active lesions or whether they merely reflect a transient response to cellular stress.



Although the exact localization and relative intensity of IL-1β expression in EAE and MS is different, the staining pattern in both neuroinflammatory disorders is most consistent with the idea that the expression of IL-1β during lesion development is induced in the tissue rather than in the periphery.
Alternatives Unit, Biomedical Primate Research Centre, Lange Kleiweg 161, 2288 GJ, Rijswijk, The Netherlands.
Saskia Maria
SM
Burm
Department of Pathology, VU Medical Center, PO Box 7057, 1007 MB, Amsterdam, The Netherlands.
Laura Anna Norma
LA
Peferoen
Alternatives Unit, Biomedical Primate Research Centre, Lange Kleiweg 161, 2288 GJ, Rijswijk, The Netherlands.
Ella Alwine
EA
Zuiderwijk-Sick
Department of Immunobiology, Biomedical Primate Research Centre, Lange Kleiweg 161, 2288 GJ, Rijswijk, The Netherlands.
Krista Geraldine
KG
Haanstra
Department of Immunobiology, Biomedical Primate Research Centre, Lange Kleiweg 161, 2288 GJ, Rijswijk, The Netherlands.
Bert Adriaan
BA
't Hart
Department of Pathology, VU Medical Center, PO Box 7057, 1007 MB, Amsterdam, The Netherlands.
Paul
P
van der Valk
Department of Pathology, VU Medical Center, PO Box 7057, 1007 MB, Amsterdam, The Netherlands.
Sandra
S
Amor
Department of Neuroimmunology, Medical University of Vienna, Spitalgasse 4, A-1090, Vienna, Austria.
Jan
J
Bauer
Alternatives Unit, Biomedical Primate Research Centre, Lange Kleiweg 161, 2288 GJ, Rijswijk, The Netherlands. bajramovic@bprc.nl.
Jeffrey John
JJ
Bajramovic
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D002135:Calcium-Binding Proteins; D040502:Calgranulin B / Q000378:metabolism; D002490:Central Nervous System / Q000378:metabolism*; D016207:Cytokines / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000378:metabolism; D004195:Disease Models, Animal; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000139:chemically induced / Q000473:pathology*; D005260:Female; D006801:Humans; D053583:Interleukin-1beta / Q000235:genetics* / Q000378:metabolism; D008253:Macaca mulatta; D008297:Male; D008840:Microfilament Proteins; D017628:Microglia / Q000378:metabolism / Q000473:pathology; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000473:pathology*; D009687:Nuclear Proteins / Q000378:metabolism; D015534:Trans-Activators / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism
C112986:AIF1 protein, human; D002135:Calcium-Binding Proteins; D040502:Calgranulin B; D016207:Cytokines; D004268:DNA-Binding Proteins; D053583:Interleukin-1beta; C083728:MHC class II transactivator protein; C078341:MYT1 protein, human; D008840:Microfilament Proteins; D009687:Nuclear Proteins; D015534:Trans-Activators; D014157:Transcription Factors
Experimental autoimmune encephalomyelitis; IL-1β; Inflammasome; Microglia; Multiple sclerosis; Preactive lesion