Adamantiades-Behcet's disease: interleukin-8 is increased in serum of patients with active oral and neurological manifestations and is secreted by small vessel endothelial cells

The serum levels of several cytokines were determined in 94 patients with A damantiades-Behcet's disease (ABD), aged 36.1 +/- 11.0 years, during the ac tive stage (n = 75) and the inactive stage (n = 19) of the disease, A group of 75 healthy individuals matched for age and sex served as controls. Cyto kine levels were determined using commercially available ELISA kits. Of the 75 patients with active disease and 19 with inactive disease, 38 (51%) and 4 (21%), respectively, and 23 healthy controls (31%) were found to have de tectable levels of interleukin 8 (IL-8) in their serum (P < 0.05). Also, in creased IL-8 serum levels were found in patients with active disease (media n 12 pg/ml, P = 0.010) compared to patients with inactive disease (less tha n or equal to 10 pg/ml) and to healthy controls (less than or equal to 10 p g/ml). In particular, patients with oral aphthous ulcers (n = 51, 34 pg/ml) and neurological features (n = 4, 71 pg/ml) exhibited increased IL-8 level s. In contrast, there was no correlation between disease activity and the s erum levels of IL-1 alpha, IL-1 beta, tumor necrosis factor alpha (TNF-alph a), soluble intercellular adhesion molecule-1 or basic fibroblast growth fa ctor (bFGF). In a second set of experiments, the involvement of dermal micr ovascular endothelial cells in IL-8 secretion was investigated. Immortalize d human dermal microvascular endothelial cells (HMEC-1 cells) were maintain ed for 4 h in vitro with serum from 18 ABD patients or with IL-1 beta, a kn own stimulator of IL-8 synthesis, TNF-alpha or their combination at five- t o tenfold higher concentrations than those found in the serum of ABD patien ts. Increased IL-8 secretion was found after incubation with ABD patients' serum (median 20 pg/ml), but IL-1 beta, TNF-alpha and IL-1 beta + TNF-alpha failed to induce IL-8 secretion by HMEC-1 cells (less than or equal to 1-1 .2 pg/ml) in biologically relevant concentrations. Our study showed increas ed IL-8 serum levels in ABD patients with active oral and neurological mani festations. Human microvascular endothelial cells may, at least partially, be responsible for the enhanced IL-8 secretion in the active stage of the d isease.