OBJECTIVE: Treatment of Behçet's disease (BD) with human recombinant interferon-alpha2a (IFN-alpha2a) has proven clinically effective. The mechanism of action is unknown. This is the first study investigating the influence of IFN-alpha2a on intracellular cytokines in T-cells in patients with BD in comparison to healthy controls and to patients with ankylosing spondylitis (AS). METHODS: Cytokine expression of T-cells was investigated in 10 patients with BD before and 4 and 12 weeks after initiation of treatment with IFN-alpha2a. 10 patients with AS and 10 healthy individuals served as controls. Peripheral blood mononuclear cells were assayed by flow cytometry for the cell surface markers CD3, CD8 and CD4 and for the intracellular cytokines interleukin 2 (IL 2), tumor necrosis factor-alpha (TNF-alpha), interferon-gamma (IFN-gamma) and interleukin 4 (IL 4). RESULTS: The fraction of CD3+ and CD4+ T-cells producing IL 2 was significantly lower in untreated BD and AS patients compared to healthy controls (p = 0.02 and 0.007). However, the number of IFN-g-producing CD3+ T-cells in untreated BD patients was elevated in comparison to both control groups (p = 0.05). T-cell cytokine analysis of BD patients revealed a significant increase of IL 2-production in T-cells during IFN-alpha2a treatment (p < 0.001). CD4+ T-cells producing IFN-gamma and TNF-alpha increased significantly (p = 0.002 and p = 0.01). CONCLUSION: In BD and AS, CD3+ and CD4+ T-cells producing IL 2 are reduced. This may hint at a similarity in the pathogenesis of these HLA-class I-associated disorders. IFN-alpha2a induces restoration of IL 2-production in patients with BD which is likely to be one mechanism of action of IFN-alpha2a.
OBJECTIVE: Treatment of Behçet's disease (BD) with human recombinant interferon-alpha2a (IFN-alpha2a) has proven clinically effective. The mechanism of action is unknown. This is the first study investigating the influence of IFN-alpha2a on intracellular cytokines in T-cells in patients with BD in comparison to healthy controls and to patients with ankylosing spondylitis (AS). METHODS: Cytokine expression of T-cells was investigated in 10 patients with BD before and 4 and 12 weeks after initiation of treatment with IFN-alpha2a. 10 patients with AS and 10 healthy individuals served as controls. Peripheral blood mononuclear cells were assayed by flow cytometry for the cell surface markers CD3, CD8 and CD4 and for the intracellular cytokines interleukin 2 (IL 2), tumor necrosis factor-alpha (TNF-alpha), interferon-gamma (IFN-gamma) and interleukin 4 (IL 4). RESULTS: The fraction of CD3+ and CD4+ T-cells producing IL 2 was significantly lower in untreated BD and AS patients compared to healthy controls (p = 0.02 and 0.007). However, the number of IFN-g-producing CD3+ T-cells in untreated BD patients was elevated in comparison to both control groups (p = 0.05). T-cell cytokine analysis of BD patients revealed a significant increase of IL 2-production in T-cells during IFN-alpha2a treatment (p < 0.001). CD4+ T-cells producing IFN-gamma and TNF-alpha increased significantly (p = 0.002 and p = 0.01). CONCLUSION: In BD and AS, CD3+ and CD4+ T-cells producing IL 2 are reduced. This may hint at a similarity in the pathogenesis of these HLA-class I-associated disorders. IFN-alpha2a induces restoration of IL 2-production in patients with BD which is likely to be one mechanism of action of IFN-alpha2a.