Treatment of experimental autoimmune uveitis in the rat with systemic succinylacetone.
The effects of succinylacetone (SA) on the development of S-antigen-induced experimental autoimmune uveitis (EAU) in the rat were studied. SA totally suppressed EAU at Day 14 when animals were treated with a constant infusion of 1.80 mg/hr by an osmotic minipump. Three intervals of treatment with this dose rate were used (Day 0-7, Day 7-14, or Day 0-14) and, regardless of dosage interval, suppression of the disease was complete. There was a significant inhibition of S-antigen-induced lymphocyte proliferative responses in cells from popliteal lymph nodes (P less than 0.009) as well as a significant decrease of S-antigen antibody production. Animals treated with SA at a rate of 0.90 or 0.45 mg/hr developed EAU in a dose-related fashion. Animals treated with 1.8 mg/hr from Day 7-14 but killed at Day 30 had 100% breakthrough of the disease. Succinylacetone inhibits the expression of EAU and significantly suppresses the immune response to S-antigen. However, once therapy is discontinued the high incidence of breakthrough suggests a reversible noncytotoxic mechanism of immune modulation.
Skolik
S A
SA
Section of Clinical Ophthalmic Immunology, National Eye Institute, Bethesda, Maryland 20892.
Palestine
A G
AG
Blaese
R M
RM
Nussenblatt
R B
RB
Hess
R A
RA
D000818:Animals; D001327:Autoimmune Diseases / Q000188:drug therapy*; D004305:Dose-Response Relationship, Drug; D005260:Female; D006537:Heptanoates / Q000627:therapeutic use*; D006538:Heptanoic Acids / Q000627:therapeutic use*; D008213:Lymphocyte Activation; D051381:Rats; D011917:Rats, Inbred Lew; D014605:Uveitis / Q000188:drug therapy* / Q000276:immunology
D006537:Heptanoates; D006538:Heptanoic Acids; C020804:succinylacetone