Treatment of autoimmune uveoretinitis in the rat with rapamycin, an inhibitor of lymphocyte growth factor signal transduction
1993; Taylor & Francis; Volume: 12; Issue: 2 Linguagem: Inglês
10.3109/02713689308999487
ISSN1460-2202
AutoresFrançois Roberge, Dasheng Xu, Chi‐Chao Chan, Marc D. de Smet, Robert B. Nussenblatt, Huifang Chen,
Tópico(s)Cell death mechanisms and regulation
ResumoRapamycin (RAPA) is a macrolide antibiotic with unique immunosuppressive properties. RAPA inhibits T-cell function by interfering with IL-2 and IL-4 signal transduction. It does not prevent IL-2 production or IL-2R expression. The efficacy of RAPA in the treatment of autoimmune diseases was evaluated using the experimental autoimmune uveoretinitis (EAU) model. EAU was actively induced in Lewis rats by immunization with S-antigen in Hunter's adjuvant. RAPA and control vehicle were administered by continuous intravenous infusion over a 14 day period by miniosmotic pump. RAPA treatment initiated on the day of immunization or 7 days later was found to efficiently inhibit EAU induction. The minimal effective dose was 0.1 mg/kg/d. EAU inhibition was correlated with reduced number of cells in the immunization site draining lymph nodes, as well as with a shift and lowering of the peak of the lymphocyte proliferative response curve. The anti-S-antigen antibody response was delayed by 3 days under RAPA treatment and the serum levels lowered in a dose dependent manner. An initial body weight loss was observed during the first week of drug administration, but there was a normal weight gain afterward.
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