Suppressive effect of transforming growth factor beta1 on the recurrence of experimental melanin protein-induced uveitis: upregulation of ocular interleukin-10.

Uveitis is induced in Lewis rats by immunization with bovine melanin protein (BMP) derived from the uvea and retinal pigment epithelium. Recurrence of this experimental melanin protein-induced uveitis (EMIU) develops after footpad injection of a minimal amount of Salmonella typhimurium endotoxin (LPS) following the remission of EMIU. To investigate the effect of transforming growth factor beta1 (TGFbeta1) on the recurrence of EMIU, 5 micrograms LPS booster was given to Lewis rats by footpad injection on Day 45 after BMP immunization. Daily TGFbeta1 or phosphate-buffered saline was administered either from Day 0 to 7 (group 1) or from Day 7 to 13 (group 2) after LPS booster. Delayed-type hypersensitivity (DTH) ear test was conducted on Day 12 after LPS booster and eye and blood were collected on Day 14. The incidence and severity of recurrent uveitis markedly decreased in both groups of TGFbeta1-treated rats. A lower level of serum BMP antibody was also observed by agglutination in these groups. There was no statistical difference in DTH responses between the treated and control groups. Ocular cytokine mRNA of group 1 and controls was analyzed by RT-PCR. Interleukin (IL)-2 and interferon-gamma were not detectable. IL-4 was identified at a similar level in both groups. A higher level of IL-10 was observed in group 1 rats. We conclude that TGFbeta1 suppresses recurrent EMIU, probably through upregulation of IL-10.