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H. Kohno, T. Sakai, S. Saito, K. Okano, K. Kitahara; Anti–Inflammatory and Immunosuppressive Effects of Atorvastatin and Lovastatin in Experimental Autoimmunue Uveoretinitis . Invest. Ophthalmol. Vis. Sci. 2006;47(13):4538.
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© ARVO (1962-2015); The Authors (2016-present)
Statins, which are 3–hydroxy–3–methyglutaryl coenzyme A (HMG–CoA) reductase inhibitors, are approved for cholesterol reduction and are commonly used to treat atherosclerosis and coronary artery disease. Statins may also be potent immunomodulatory agents and may be beneficial in the treatment of autoimmunue diseases. We investigated the effects of atorvastatin and lovastatin on experimental autoimmunue uveoretinitis (EAU).
EAU was induced in Lewis rats with S antigen. Atorvastatin was suspended in 0.5% aqueous methylcellulose and was administered orally in 0.5 ml methylcellulose (10 mg/kg) once daily for 14 days from the appearance of clinical signs. Lovastatin was dissolved in DMSO: PBS (1:1) was administered daily by i.p. injection at a dose of 2 mg/kg. The clinical scores and delayed type hypersensitivity (DTH) were evaluated 14 days after the administration. Morphologic and immunohistochemical examinations with a confocal microscope were performed in all rats. Lymphocyte proliferation was measured by [3H]thymidine incorporation by antigen–stimulated T cells from inguinal lymph nodes. After 72 hours, supernatants were collected and assayed for IFN–γ by ELISA kits.
Clinical and histological scores of EAU were decreased in both atorvastatin–treated and lovastatin–treated groups. The invasion of T cells, macrophages, the proliferation of Müller cells, the expression of MHC ClassII were inhibited in both groups. DTH of both groups was significantly inhibited compared with that of controls (p=0.0004 and p= 0.005, respectively). Lymphocyte proliferation assay showed a decreased lymphocyte proliferation in the presence of 25, and 5 µg/ml S–Ag in both groups compared with controls. In the supernatants of lymph node cells stimulated with S–Ag (5 µg/ml), 77% or 87% inhibition of IFN–γ production was found in rats treated with atorvastatin or lovastatin, respectively, compared with controls.
Both atorvastatin and lovastatin showed significant anti–inflammatory and immunosuppressive effects in EAU. Statins may be useful for treating intraocular inflammation.
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