Study On The Effect Of Tolerance Induced Via Enema On Inhibiting Experimental Autoimmune Uveoretinitis

Objective: To investigate the feasibility of the induction of mucosal tolerance viaenema administration of bovine retinal soluble-antigen (S-Ag) to inhibit experimental autoimmune uveoretinitis (EAU) induced with human soluble-antigen peptide 35 (SP35).Methods: All Lewis rats, except controls, were pretreated to induce mucosaltolerance, with oral or enema administration of five 2 mg or 0.2 mg doses of bovine retinal S-Ag at day -10, -8, -6, -4 and -2, before being immunized two times (0.1 mg each) in the hind foot-pads at day 0 and 7 with SP35 emulsified in completeFreund's adjuvant (CFA);After the second EAU induction, all rats were monitored daily by grading the clinical score of EAU until at day 21 they were killed, and their eyes were removed for histopathological examination, serum was collected and tested in EUSA for the presence of antibodies against retinal S-Ag and SP35, spleens were also removed for RT-PCR analysis of IL-4 mRNA |P IFN-y mRNA expression.Results: (1) The animal model of EAU could be successfully induced byimmunizing Lewis rats with SP35 emulsified in CFA, and its incidence rate was surprisingly 100%. (2) Mucosal tolerance induced by oral or enema administration of multiple doses of bovine retinal S-Ag before active immunization could significantly inhibit the development of EAU induced with human SP35 in a dose dependent manner, found in delaying the day of onset-time and the day of peak-time, shortening the time of duration and reducing the severity of disease, while not found in the incidence rate of EAU;What's more, the tolerance induced via enema was more effective than the oral. (3) there was no significantly difference in the level of serum antibodies among treated groups, but superior to the normal. (4) Unexpectedly, there was also no significantly difference in the level of spleen IL-4 mRNA fP IFN-y mRNA expression between groups.Conclusions: Induction of mucosal tolerance via enema administration of autoantigens was a safe and effective way to inhibit EAU.