Combined cyclosporin-A /prednisone therapy of patients with active uveitis suppresses IFN-gamma production and the function of dendritic cells.
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.
Frassanito
M A
MA
Department of Biomedical Sciences and Human Oncology, Section of Internal Medicine and Clinical Oncology, University of Bari Medical School, Bari, Italy. mfrassanito@hotmail.com
Dammacco
R
R
Fusaro
T
T
Cusmai
A
A
Guerriero
S
S
Sborgia
C
C
D000328:Adult; D002908:Chronic Disease; D016572:Cyclosporine / Q000627:therapeutic use*; D003713:Dendritic Cells / Q000187:drug effects* / Q000276:immunology; D004359:Drug Therapy, Combination; D005260:Female; D005500:Follow-Up Studies; D005938:Glucocorticoids / Q000627:therapeutic use; D006801:Humans; D016130:Immunophenotyping; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D007371:Interferon-gamma / Q000096:biosynthesis*; D016753:Interleukin-10 / Q000097:blood; D018664:Interleukin-12 / Q000097:blood; D007959:Lymphocyte Culture Test, Mixed; D008297:Male; D008875:Middle Aged; D011241:Prednisone / Q000627:therapeutic use*; D018417:Th1 Cells / Q000276:immunology; D014605:Uveitis / Q000188:drug therapy* / Q000276:immunology
D005938:Glucocorticoids; D007166:Immunosuppressive Agents; D016753:Interleukin-10; D018664:Interleukin-12; D007371:Interferon-gamma; D016572:Cyclosporine; D011241:Prednisone