OBJECTIVETo study the mechanism of prophylactic effects of nasal tolerance with a dual analogue (Lys262-Ala207) on experimental autoimmune myasthenia gravis (EAMG).

METHODSClinical and immunological changes were observed in Lewis rats administered with dual analogue Lys262-Ala207 nasally, to compare the effects between the rats with predetermined dosage of Lys262-Ala207 and control peptides at two different time points, before the day (Group A or C) or on the day (Group B or D) of immunization with acetylcholine receptor (AChR) in complete Freud's adjuvant for 10 consecutive days. The clinical scores was evaluated for 50 days post immunization. Numbers of MNC expressing IFN-gamma, IL-4 or IL-10 and CD4+ and/or CD25+ from lymph nodes were enumerated by flow cytometry. Proliferative response, expressed as stimulation index (SI), was suppressed in response to antigen-specific stimulation in the rats receiving dual analogue, as compared with the rats receiving saline buffer only.

RESULTSGroup A and group B of Lewis rats developed EAMG with reduced severity, as compared to the control groups. Number of cells synthesizing IFN-gamma, IL-4 or IL-10 decreased, whereas numbers of CD4+CD25+ cells increased in group A and B than those in the control groups. Proliferative response was suppressed in response to antigen-specific stimulations in the rats receiving dual analogue Lys262-Ala207.

CONCLUSIONSNasal administration with a dual analogue Lys262-Ala207 at two different time points, before the day and on the day of immunization, could delay symptoms of muscular weakness in EAMG rats, which was associated with suppression of immune function in AChR antigen-specific T cells and lay a scientific foundation for treatment of human MG with nasal dual analogue.