Subcutaneous Administration of Engineered Interleukin-10 Prevents Experimental Autoimmune Encephalomyelitis by Promoting Immunoregulation in the Secondary Lymphoid Organs and Spinal Cord 9102

Abstract Description Interleukin 10 (IL-10) is an immunoregulatory cytokine known to suppress pro-inflammatory cytokine production, inhibit T cell activation, reduce antigen presentation, and promote M2-macrophage polarization. However, its clinical use is hindered by short plasma half-life and poor retention in the secondary lymphoid organs (SLOs), sites of T cell priming in autoimmunity. To address these limitations, we previously engineered a fusion protein of serum albumin and IL-10 (SA IL-10) with extended half-life and enhanced retention in the SLOs. Here, we evaluate subcutaneously administered SA IL-10 as a therapy for experimental autoimmune encephalomyelitis (EAE), a murine model of multiple sclerosis (MS). We show that SA IL-10 treatment prevents the development and progression of EAE with superior efficacy to wild type IL-10 and comparable efficacy to FTY 720, an FDA-approved MS drug. In the SLOs, SA IL-10 reduced disease-associated antigen-specific TH17 T cells, M1-polarized macrophages, activated dendritic cells and pro-inflammatory cytokine production, while expanding immunoregulatory M2-polarized macrophages. SA IL-10 also suppressed macrophage and dendritic cell infiltration in the spinal cord. Notably, SA IL-10 treated EAE-bearing mice maintained healthy body weight and serum biochemistry markers comparable to saline-treated mice, indicating no evidence of organ toxicity. Our findings suggest that SA IL-10 is a safe and effective therapeutic for neuroinflammatory diseases. Topic Categories Neuroimmunology (NEUR)