Features of systemic cytokine production in Behcet's disease associated with uveitis without ocular lesions

Behcet's disease (BD) is a systemic disease underlyed by chronic vasculitis. Hyperactivity of innate and adaptive immunity plays important role in its pathogenesis. Uveitis occurs in 30-70% of the patients, often recurring and reducing visual function. The objective of our work was to study the features of systemic production of immune mediators in BD patients, depending on presence and activity of uveitis. 116 BD patients were divided into 3 groups: (1) 41 patients with active uveitis (UA), (2) 64 subjects with uveitis remission (UR), (3) 11 uveitis-free BD patients (WU). Control group (CG) comprised 34 conditionally healthy people. Detection rate (%) and contents (pg/ml) were measured for IL-1β IL-2, IL-4, IL-5, IL-6, IL-12p70, IL-13, IL-18, IFNγ, CCL2/MCP-1, CCL3/MIP-1α, CCL4/MIP-1β, CCL5/RANTES, CCL11/Eotaxin, СXCL1/GRO-α, CXCL8/IL-8, CXCL10/IP-10, CXCL12/SDF-1α, GM-CSF, TNFα in blood serum by means of multiplex analysis using MAGPIX analyzer (Luminex Corp., USA), Procarta Plex “Human Th1/Th2&Chemokine Panel 20 plex” kits (Bioscience, Austria). TGF-P1, TGF-P2 levels were assayed by ELISA-test (“Vfector-Best”). All the BD patients showed high detection rates of CXCL1/GRO-α (but not its level) in comparison with CG. Detection rate and levels of IL-6, IL-8 were increased in 1^st and 2^nd BD groups, compared to CG. In UR, unlike UA and WU groups, IL-4 was detected more often than in CG. WU patients showed increased detection rate of only CXCL1/GRO -α. When compared with UA, WU patients had lower serum concentrations of IFNγ, MCP-1, IP-10, MIP-1a, SDF-1α, TGF-β1; UR patients also showed decreased serum levels of IL-18, Eotaxin, GRO-α, RANTES, TGF-β2. Our results indicate the importance of angiogenic and proinflammatory chemokines and cytokines in pathogenesis of BD uveitis, as well as imbalanced production of various immunomediators. Higher detection rates and levels of IL-6 and IL-8 in UA and UR patients may result from weak persistent intraocular inflammation, even upon relief of clinical symptoms, thus, probably, requiring therapeutic correction.

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