Cytokine production profile in patients with Behcet's disease treated with infliximab

Although the etiology of Behcet's disease (BD) still remains uncertain, various immune abnormalities have been implicated in BD. We studied cytokine production in patients with active and inactive BD, and evaluated the effect of treatment with infliximab (anti-TNF-α antibody) on disease activity and cytokine production by the ELISPOT assay. The numbers of cells spontaneously secreting IFN-γ, IL-12, and TNF-α were significantly increased in patients with active BD. Mitogen-stimulated IL-4 secretion was elevated in active patients, though the ratio of IFN-γ:IL-4 secreting cells was significantly increased in active BD. Next, we monitored cytokine production and expression of IL-12 receptor β1 chain (IL-12Rβ1) during short- and long-term infliximab treatment. A single infusion of infliximab significantly reduced the number of PBMC secreting TNF-α within 24 h. A rise in TNF-α production was associated with clinical deterioration. Infliximab treatment induced a significant increase in the number of cells secreting IFN-γ and expressing IL-12Rβ1. A favorable clinical response to infliximab was associated with a persistent reduction in TNF-α secretion, but did not correlate with IFN-γ production. Our findings indicate that TNF-α plays a pivotal role in BD, and that anti-TNF-α therapy both reduces TNF-α production and modulates the functional activity of type 1 cells.