Combined cyclosporin-A /prednisone therapy of patients with active uveitis suppresses IFN-gamma production and the function of dendritic cells |
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Authors: | Frassanito M A Dammacco R Fusaro T Cusmai A Guerriero S Sborgia C |
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Institution: | Department of Biomedical Sciences and Human Oncology, Section of Internal Medicine and Clinical Oncology, University of Bari Medical School, Bari, Italy. mfrassanito@hotmail.com |
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Abstract: | In this study, we assessed the Th1/Th2 polarization of the immune response and the involvement of dendritic cells (DC) and Th1 lymphocytes in the pathogenesis of uveitis. Thirty-seven patients with chronic idiopathic uveitis were enrolled: 21 of them had active uveitis and the remaining 16 were in complete remission. Patients with active uveitis were characterized as follows: 5 had intermediate uveitis, 5 panuveitis and the remaining 11 posterior uveitis. Thirteen healthy subjects were also studied as controls. Patients with active uveitis were treated with cyclosporin-A (CsA) associated to low doses of prednisone (PDS) and studied at baseline and after 6 months of therapy. Analysis of cytokine-producing CD3+ lymphocytes revealed a strong Th1 polarization of the immune response in patients with active uveitis. Th1 lymphocytes paralleled serum IL-12 levels and the response to therapy, which greatly reduced both IFN-gamma+/CD3+ lymphocytes and serum IL-12 levels, associated with a general clinical improvement. In vitro studies demonstrated that DC from untreated patients with active uveitis were mature and functionally active. In fact, they showed a higher ability to stimulate cell proliferation of allogeneic T cells in primary mixed lymphocyte reaction (MLR) and produced larger amounts of IL-12 than DC from CsA/PDS-treated patients and those in remission. These results demonstrate that CsA/PDS therapy impairs the capacity of mature DC to secrete IL-12 and inhibits their MLR activity. |
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Keywords: | cyclosporin‐A prednisone therapy dendritic cells IL‐12 Th1 Th2 lymphocytes uveitis |
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