IL-6 Inhibition as a Therapeutic Target in Aged Experimental Autoimmune Encephalomyelitis.
María DemaHerena EixarchMireia CastilloXavier MontalbanCarmen EspejoPublished in: International journal of molecular sciences (2024)
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) 35-55 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.
Keyphrases
- multiple sclerosis
- mass spectrometry
- immune response
- spinal cord
- end stage renal disease
- ms ms
- newly diagnosed
- ejection fraction
- traumatic brain injury
- peritoneal dialysis
- dna damage
- clinical trial
- dendritic cells
- risk assessment
- adipose tissue
- prognostic factors
- inflammatory response
- double blind
- climate change
- brain injury
- lps induced
- combination therapy
- human health
- smoking cessation
- stress induced
- placebo controlled
- study protocol