Abstract
BackgroundInterleukin (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.MethodsHere, 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.ResultsIn 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.ConclusionsAlthough 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.Electronic supplementary materialThe online version of this article (doi:10.1186/s12974-016-0605-8) contains supplementary material, which is available to authorized users.
Highlights
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
Rhesus EAE We studied brain tissue from three rhesus macaques without neurological disease and from 12 rhesus macaques that were immunized with rhMOG in either incomplete Freund’s adjuvant (IFA) or complete Freund’s adjuvant (CFA), of which eight animals developed clinical EAE (Table 1)
As IFA does not contain mycobacteria that were previously shown to be involved in IL-1β production [60], we studied the expression of IL1β in brain tissue of animals immunized with rhMOG in CFA
Summary
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. NLR associate with inflammatory caspases, mostly via the adaptor protein ASC, leading to processing and secretion of proinflammatory cytokines such as IL-1β and IL-18 [19, 20]. The involvement of IL-1β and the inflammasome in experimental autoimmune encephalomyelitis (EAE), a commonly used animal model for MS, has been confirmed in different studies [21]. Expression levels of IL-1β [29,30,31], specific NLRs (e.g., NLRP1 and NLRP3) and caspase 1 are increased in the brain and spinal cord during disease [26, 32]. Treatment with interferon (IFN)β, a registered therapeutic biological for MS [34], decreases brain pathology by reducing serum IL-1β and caspase 1 activation levels [35]
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