Interferon-alpha: a key factor in autoimmune disease?
OBJECTIVE
Interferon (IFN)-alpha is an effective drug for treatment of uveitis in Behçet's disease. This study was undertaken to investigate the mechanism of action of IFN-alpha in the treatment of various types of noninfectious sight-threatening uveitis.


METHODS
Eleven patients with refractory uveitis, and 13 healthy individuals were enrolled. The number of circulating plasmacytoid dendritic cells (pDCs) and their capacity to produce IFN-alpha in culture on stimulation with synthetic oligodinucleotides containing the CpG-motif were studied. Peripheral blood CD4+ T-cell phenotype and activation status were evaluated by flow cytometry at 0, 2, and 8 weeks after treatment for expression of CD69, CD62L, chemokine receptors (CCR4, CXCR3, and CCR5), and intracellular cytokines (TNF-alpha, IFN-gamma, and IL-10).


RESULTS
All patients experienced a positive clinical response to IFN-alpha treatment. There was no significant difference between patients and control subjects in the number of circulating pDCs, but there was a significant decrease in the capability of patients' pDCs to produce IFN-alpha in response to CpG (P < 0.001). Peripheral blood CD4+ T cells expressed reduced levels of surface CD62L (P < 0.005) as a measure of activation and higher levels of chemokine receptors CXCR3, CCR4, and CCR5 (P < 0.005, P < 0.05, and P < 0.05, respectively); in addition, intracellular T-cell IL-10 levels were increased once the treatment was initiated (P < 0.01).


CONCLUSIONS
The data suggest that IFN-alpha may control uveitis by promoting induction of IL-10-producing T-cells, possibly T-regulatory cells. Dysregulation of the T-cell population in patients with uveitis may be associated with a defect in the pDCs' ability to produce IFN-alpha, which can be circumvented with administration of exogenous IFN-alpha.
Plskova
Jarka
J
Department of Ophthalmology, University of Aberdeen, Aberdeen, Scotland, United Kingdom.
Greiner
Kathrin
K
Muckersie
Elizabeth
E
Duncan
Linda
L
Forrester
John V
JV
D000293:Adolescent; D000328:Adult; D015703:Antigens, CD / Q000378:metabolism; D000945:Antigens, Differentiation, T-Lymphocyte / Q000378:metabolism; D001327:Autoimmune Diseases / Q000188:drug therapy* / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018929:Cell Culture Techniques; D016207:Cytokines / Q000378:metabolism; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D016130:Immunophenotyping; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000096:biosynthesis / Q000627:therapeutic use*; D019041:L-Selectin / Q000378:metabolism; D037181:Lectins, C-Type; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D019707:Receptors, Chemokine / Q000378:metabolism; D011994:Recombinant Proteins; D015866:Uveitis, Posterior / Q000188:drug therapy* / Q000276:immunology; D000099192:CD69 Antigens
D015703:Antigens, CD; D000945:Antigens, Differentiation, T-Lymphocyte; D016207:Cytokines; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D019041:L-Selectin; D037181:Lectins, C-Type; D019707:Receptors, Chemokine; D011994:Recombinant Proteins; D000099192:CD69 Antigens