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K.G. Ooi, G. Galatowicz, V.L. Calder, S. Lightman; The Immunomodulatory Effects of HMG–CoA Reductase Inhibitors (Statins): Atorvastatin Downregulates IFN– and TNF and Potentiates the Immunosuppressive Effects of Dexamethasone on Human T cells . Invest. Ophthalmol. Vis. Sci. 2006;47(13):4539.
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© ARVO (1962-2015); The Authors (2016-present)
To investigate the immunomodulatory potential of atorvastatin (A), lovastatin (L) and simvastatin (S) in comparison with cyclosporine A (CsA), rapamycin (R) mycophenolate (M) and dexamethasone (D) on cytokine responses and proliferation of human T cells.
Peripheral venous blood was obtained from 16 healthy donors. For viability and proliferation assays mononuclear cells were isolated, labeled with 5,6–carboxyfluorescein diacetate succinimidyl ester (CFSE) and cultured for 5 days with anti–CD3 + –CD28 mAb with or without drugs. Propidium iodide (PI) added prior to flow cytometric analysis. 18h–PMA/ionomycin stimulated whole blood was used for multiplex cytokine detection conducted on supernatants for IL–1ß, IL–2, IL–4, IL–5, IL–6, IL–8, IL–10, IFN–γ, TNFα and TNFß, and intracellular cytokine staining for IL–2, IL–4, IL–10 and IFN–γ was also performed.
Significant inhibition of T cell proliferation was achieved by A, L, S at 10–100µM (P < 0.05); R, M at 50–100µM (P < 0.05); D at 100–800µg/ml (P < 0.01) in response to anti–CD3/28 mAb; CsA at 250–500ng/ml (P < 0.05) with anti–CD3 mAb only, without significantly affecting viability (PI–). Significant decreases in cytokine production were detected in the presence of drugs: IFN–γ and TNFα with A (P < 0.05); IL–6 and TNFα with L (P < 0.05); IFN–γ and TNFα with CsA and D (P < 0.01); TNFα and IL–6 with M (P < 0.05) but not R. D combined with A significantly decreased IL–1ß (P < 0.05), IL–2, IL–6, IFN–γ and TNFα (all P < 0.01). Significant increases were detected for: IL–10 by D (P < 0.01) and IL–4 by D combined with A (P < 0.05). Intracellular cytokine staining showed decreases in IFN–γ expression by A, L and S (P < 0.01).
Aside from their established cholesterol–lowering effects, statins also exert immunomodulatory effects, further confirmed by these results. Statins have potential as part of combination immunotherapy in the treatment of Th–1 mediated immune diseases, including multiple sclerosis, rheumatoid arthritis and uveitis.
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