Synergism between corticosteroids and Rapamycin for the treatment of intraocular inflammation

Abstract

The authors studied the combination effect of corticosteroids with the new immunosuppressant Rapamycin for the treatment of intraocular inflammation. A median-effect analysis, of the combined effect of Rapamycin and dexamethasone, was performed on the inhibition of lymphocyte proliferation in culture. The mathematical formulas allowed for the calculation of combination indices and dose-reduction factors. On the basis of these in-vitro results, treatment with reduced doses of drugs in combination was evaluated in the rat model of experimental autoimmune uveoretinitis. The results showed that Rapamycin and dexamethasone were synergistic over a wide concentration range. The calculated dose reduction factors indicated that an equivalent inhibition of lymphocyte proliferation was achieved with a combination of Rapamycin and dexamethasone reduced by 5-7 and 3-6 fold respectively, compared to the concentration required when each drug was used alone. In animals, there was a significant reduction of the incidence and severity of ocular inflammation with low doses of the drugs in combination. The authors conclude that the observed synergistic effect between Rapamycin and dexamethasone suggests that the use of this drug combination might be advantageous in the treatment of patients with severe uveitis.