Expression of IL-1β in rhesus EAE and MS lesions is mainly induced in the CNS itself

Background: Interleukin (IL)-1 beta 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)-1 beta expression in different stages of MS lesion development and a comparison of (IL)-1 beta expression in MS and EAE are lacking. Methods: Here, we performed an extensive characterization of (IL)-1 beta expression in brain tissue of MS patients, which included different MS lesion types, and in brain tissue of rhesus macaques with EAE. Results: In rhesus EAE brain tissue, we observed prominent (IL)-1 beta 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)-1 beta expression is induced within the central nervous system (CNS). By contrast, (IL)-1 beta 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)-1 beta 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)-1 beta(+) nodules are destined to progress into active lesions or whether they merely reflect a transient response to cellular stress. Conclusions: Although the exact localization and relative intensity of (IL)-1 beta 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)-1 beta during lesion development is induced in the tissue rather than in the periphery.