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IL-6 Inhibition as a Therapeutic Target in Aged Experimental Autoimmune Encephalomyelitis Dema, María Eixarch, Herena Castillo Juárez, Mireia Montalban, Xavier Espejo, Carmen Universitat Autònoma de Barcelona Experimental autoimmune encephalomyelitis IL-6 Immunosenescence Ageing Innate immunity Multiple sclerosis Multiple sclerosis (MS) onset at an advanced age is associated with a higher risk of developing progressive forms and a greater accumulation of disability for which there are currently no effective disease-modifying treatments. Immunosenescence is associated with the production of the senescence-associated secretory phenotype (SASP), with IL-6 being one of the most prominent cytokines. IL-6 is a determinant for the development of autoimmunity and neuroinflammation and is involved in the pathogenesis of MS. Herein, we aimed to preclinically test the therapeutic inhibition of IL-6 signaling in experimental autoimmune encephalomyelitis (EAE) as a potential age-specific treatment for elderly MS patients. Young and aged mice were immunized with myelin oligodendrocyte protein (MOG) and examined daily for neurological signs. Mice were randomized and treated with anti-IL-6 antibody. Inflammatory infiltration was evaluated in the spinal cord and the peripheral immune response was studied. The blockade of IL-6 signaling did not improve the clinical course of EAE in an aging context. However, IL-6 inhibition was associated with an increase in the peripheral immunosuppressive response as follows: a higher frequency of CD4 T cells producing IL-10, and increased frequency of inhibitory immune check points PD-1 and Tim-3 on CD4 + T cells and Lag-3 and Tim-3 on CD8 + T cells. Our results open the window to further studies aimed to adjust the anti-IL-6 treatment conditions to tailor an effective age-specific therapy for elderly MS patients. 2024 Article https://ddd.uab.cat/record/299030 urn:10.3390/ijms25126732 urn:oai:ddd.uab.cat:299030 urn:pmcid:PMC11204061 urn:pmc-uid:11204061 urn:oai:pubmedcentral.nih.gov:11204061 urn:pmid:38928437 urn:oai:egreta.uab.cat:publications/b7e78a99-2ecd-46a9-ab75-fe37a246163b eng Instituto de Salud Carlos III PI18/01146 International journal of molecular sciences ; Vol. 25 (june 2024) open access Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original. https://creativecommons.org/licenses/by/4.0/ application/pdf