Pharmacological modulation of IgE-dependent mast cell degranulation in experimental autoimmune uveoretinitis.
Immediate hypersensitivity phenomena have been shown previously to occur at the beginning of experimental autoimmune uveoretinitis (EAU) induced in Lewis rats by immunization with purified S-antigen from bovine retina. The onset time and severity of the disease were modified by modulating the mast cell (MC) function. Drugs blocking the release of mediators from MC, disodium cromoglycate and ketotifen, given as eyedrops, slightly delayed the onset and decreased the severity of inflammation. Compound 48/80, a drug effective in depleting MC of their inflammatory mediators, delayed significantly the onset, decreased and sometimes suppressed EAU, when given by the subconjunctival or intraperitoneal routes. No modification of the IgG and the IgE circulating anti-S-antibody level was demonstrated in both types of treatment, whereas in vitro reagin-dependent degranulation of peritoneal MC in the presence of the antigen was decreased in both cases. Identification of MC-bound reagins as IgE was strongly suggested by the blocking effect of anti-IgE antibodies on MC degranulation. These data confirm the link between MC activation and the onset and severity of EAU.
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology* / Q000627:therapeutic use; D001327:Autoimmune Diseases / Q000276:immunology; D004205:Cromolyn Sodium / Q000494:pharmacology; D006969:Hypersensitivity, Immediate / Q000209:etiology; D007073:Immunoglobulin E / Q000276:immunology*; D007665:Ketotifen / Q000494:pharmacology; D008407:Mast Cells / Q000187:drug effects / Q000276:immunology*; D051381:Rats; D011917:Rats, Inbred Lew; D012173:Retinitis / Q000188:drug therapy / Q000276:immunology*; D014605:Uveitis / Q000188:drug therapy / Q000276:immunology*; D003189:p-Methoxy-N-methylphenethylamine / Q000494:pharmacology
D000893:Anti-Inflammatory Agents; D007073:Immunoglobulin E; D003189:p-Methoxy-N-methylphenethylamine; D004205:Cromolyn Sodium; D007665:Ketotifen