Tacrolimus-rapamycin combination therapy for experimental autoimmune uveoretinitis
| Autor: | Kotaro Eto, Naofumi Hikita, Manabu Mochizuki, Eiko Ikeda |
|---|---|
| Rok vydání: | 1998 |
| Předmět: |
Male
Combination therapy medicine.medical_treatment T cell T-Lymphocytes Intraperitoneal injection chemical and pharmacologic phenomena Polyenes Pharmacology Lymphocyte Activation Tacrolimus Autoimmune Diseases Immune system Medicine Animals Autoimmune disease Sirolimus Chemotherapy Arrestin business.industry Retinitis Uveitis Posterior General Medicine Drug interaction medicine.disease Rats Ophthalmology Disease Models Animal surgical procedures operative medicine.anatomical_structure Rats Inbred Lew Immunology Drug Therapy Combination Immunization business Immunosuppressive Agents Injections Intraperitoneal |
| Zdroj: | Japanese journal of ophthalmology. 41(6) |
| ISSN: | 0021-5155 |
| Popis: | Tacrolimus and rapamycin both belong to a new family of immunosuppressants, immunophilin ligands, but the mechanisms by which they inhibit T cell activation are different. Therefore, we tested the immunosuppressive effects of combination therapy with low doses of tacrolimus and rapamycin on experimental autoimmune uveoretinitis (EAU) in rats. Male Lewis rats, immunized with S-antigen (SAg) were given intraperitoneal injection of the combined drugs for 14 days after the immunization with SAg. Effects were evaluated by clinical observations, histological examination and immune response. The combination therapy with tacrolimus (0.1 mg/kg per day) and rapamycin (0.03 mg/kg per day) achieved 100% suppression of clinical EAU and 66.7% suppression of histological EAU; tacrolimus combined with a higher dose of rapamycin (0.1 mg/kg per day) caused 100% suppression clinically and histologically. Therapy with either drug alone achieved only partial suppression: tacrolimus alone (0.1 or 0.2 mg/kg per day) or rapamycin alone (0.03-0.2 mg/kg per day). Doubling the dose of either drug produced only 16.7% suppression with rapamycin or 50% suppression with tacrolimus. The serum antibody levels to SAg and proliferative response of lymphocytes to SAg were also significantly suppressed by the combination therapy with low doses of tacrolimus and rapamycin. |
| Databáze: | OpenAIRE |
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