Prophylactic administration of PEPITEM in experimental autoimmune encephalomyelitis delays disease onset, inhibits leukocyte infiltration, and alleviates severity.

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Multiple sclerosis (MS) is a chronic, immune-mediated neurological disorder in which the immune system mistakenly attacks the myelin sheath, affecting the communication between the brain and the rest of the body. This study investigated the prophylactic use of peptide inhibitor of trans-endothelial migration (PEPITEM), a novel peptide, in alleviating experimental autoimmune encephalomyelitis (EAE), a mouse model for Multiple Sclerosis (MS). Female C57BL/6 female mice were assigned to the control, untreated EAE, or PEPITEM group. EAE was induced in mice in the untreated EAE and PEPITEM groups through immunization by injecting an emulsion containing myelin oligodendrocyte glycoprotein 35-55 in complete Freund's adjuvant. Mice in these groups subsequently received PEPITEM or scramble peptide injections daily for 21 days. Then, all mice were euthanized to obtain samples for histologic and immunohistochemical analyses of central nervous system lymphocytic infiltrate. Levels of biomarkers, including myelin basic protein, microtubule-associated protein 2 (MAP-2), interleukin-17 (IL-17), and forkhead box P3 (Foxp3), were evaluated in both serum and spinal cord lysates using western blotting and enzyme-linked immunosorbent assay. In the PEPITEM group, EAE onset was significantly delayed and disease severity was reduced compared to the untreated EAE group. Analysis of spinal cord tissues revealed a marked reduction in inflammatory cell infiltration following PEPITEM administration. Furthermore, PEPITEM treatment led to significantly reduced IL-17 and Foxp3 levels, highlighting its potential in mitigating inflammatory responses. PEPITEM has potent prophylactic potential against MS, providing a robust foundation for further exploration.