Combined Nasal Administration of Encephalitogenic Myelin Basic Protein Peptide 68–86 and IL-10 Suppressed Incipient Experimental Allergic Encephalomyelitis in Lewis Rats

Mucosal administration of low doses of myelin basic protein (MBP) peptide 68–86 (MBP 68–86) or anti-inflammatory cytokine IL-10 effectively prevented experimental allergic encephalomyelitis (EAE), but failed to suppress the disease if given after 7 days postimmunization (p.i.), i.e., after T cell priming had occurred. We anticipated that combined administration of autoantigen and IL-10 can treat incipient EAE. Lewis rats with EAE actively induced with MBP 68–86 and complete Freundʹs adjuvant received 120 μg MBP 68–86 + 200 ng IL-10 per rat per day from day 7 p.i. and for 5 consecutive days. These rats showed later onset, lower clinical scores, less body weight loss, and shorter duration of EAE than rats receiving MBP 68–86 or IL-10 only or PBS. EAE amelioration was associated with decreased infiltration of ED1+ macrophages and CD4+ T cells within the central nervous system and with decreased proliferative responses of lymph node cells, indicating that combined administration of MBP 68–86 and IL-10 induced immune hyporesponsiveness. IFN-γ secretion as well as IFN-γ, TNF-α, IL-4, and IL-10 mRNA expression by lymph node MNC was down-regulated in the treated rats. Immune hyporesponsiveness, rather than immune deviation or regulatory mechanisms, seems to be responsible for the protection of EAE after autoantigen + IL-10 administration by the nasal route.