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Interferon-: A Key Factor in Autoimmune Disease?

From the Department of Ophthalmology, University of Aberdeen, Aberdeen, Scotland, United Kingdom.

PURPOSE. Interferon (IFN)- is an effective drug for treatment of uveitis in Behçet’s disease. This study was undertaken to investigate the mechanism of action of IFN- 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- 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-, IFN-, and IL-10).

RESULTS. All patients experienced a positive clinical response to IFN- 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- 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- 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-, which can be circumvented with administration of exogenous IFN-.