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-alpha antibody) on disease activity and
cytokine production by the ELISPOT assay. The numbers of cells spontaneously secreting IFN-gamma,
IL-12, and
TNF-alpha were significantly increased in patients with active BD.
Mitogen-stimulated
IL-4 secretion was elevated in active patients, though the ratio of IFN-gamma:IL-4 secreting cells was significantly increased in active BD. Next, we monitored
cytokine production and expression of
IL-12 receptor beta1 chain (IL-12Rbeta1) during short- and long-term
infliximab treatment. A single infusion of
infliximab significantly reduced the number of PBMC secreting
TNF-alpha within 24 h. A rise in
TNF-alpha production was associated with
clinical deterioration.
Infliximab treatment induced a significant increase in the number of cells secreting IFN-gamma and expressing IL-12Rbeta1. A favorable clinical response to
infliximab was associated with a persistent reduction in
TNF-alpha secretion, but did not correlate with IFN-gamma production. Our findings indicate that
TNF-alpha plays a pivotal role in BD, and that anti-
TNF-alpha therapy both reduces
TNF-alpha production and modulates the functional activity of type 1 cells.