Precipitation of experimental autoallergic uveoretinitis by cyclosporin A withdrawal: an experimental model of uveitis relapse.
This study set out to determine whether withdrawal of cyclosporin A (CyA) in Lewis rats sensitized to retinal S antigen would precipitate experimental autoallergic uveoretinitis (EAU), and whether challenge of such animals with S antigen or an unrelated stimulus would accelerate EAU onset after drug withdrawal. Rats were sensitized with 50 micrograms S antigen in Freund's complete adjuvant (FCA) and EAU onset was suppressed by 18 days of treatment with CyA at doses ranging from 3 to 10 mg/kg daily. Without challenge, seven out of 11 animals developed EAU with a median onset of 78 days. This was reduced to 68 days in rats challenged on day 32 with FCA alone, to 48 days with 10 micrograms S antigen in FCA, and to 41 days with 50 micrograms S antigen in FCA. The incidence, onset and severity of anterior uveitis and extent of photoreceptor destruction were related to both CyA dose and nature of challenge. The extent of photoreceptor destruction ran parallel with severity of anterior uveitis; and delayed-type hypersensitivity reactivity on day 43 was related to both severity of anterior uveitis (P less than 0.001) and photoreceptor damage (P less than 0.002). At the highest dose, CyA also delayed the appearance of antibody to S antigen; however, subsequent antibody levels were unrelated to EAU severity or to nature of challenge. The results indicate that CyA-induced suppression of the immunological response to S antigen can recover spontaneously after drug withdrawal, that challenge with either S antigen or FCA alone can accelerate the subsequent onset of EAU, and that these phenomena may provide a basis for investigating mechanisms underlying relapse of human uveoretinitis.
Atkinson
E G
EG
Department of Immunology, United Medical School, St Thomas' Campus, London, England.
Dinning
W J
WJ
Kasp
E
E
Graham
E M
EM
Dumonde
D C
DC
D000818:Animals; D000941:Antigens / Q000276:immunology; D019393:Arrestin; D001324:Autoantigens / Q000276:immunology; D001327:Autoimmune Diseases / Q000188:drug therapy* / Q000276:immunology; D003524:Cyclosporins / Q000627:therapeutic use*; D004195:Disease Models, Animal; D005136:Eye Proteins / Q000276:immunology; D006968:Hypersensitivity, Delayed; D008297:Male; D008565:Membrane Proteins / Q000276:immunology; D051381:Rats; D012008:Recurrence; D012173:Retinitis / Q000188:drug therapy* / Q000276:immunology; D014606:Uveitis, Anterior / Q000188:drug therapy* / Q000276:immunology
D000941:Antigens; D019393:Arrestin; D001324:Autoantigens; D003524:Cyclosporins; D005136:Eye Proteins; D008565:Membrane Proteins