High levels of interleukin-8, soluble CD4 and soluble CD8 in bullous pemphigoid blister fluid. The relationship between local cytokine production andlesional T-cell activities

Background Bullous pemphigoid (BP) is an inflammatory subepidermal blisteri ng disease associated with autoantibodies that recognize hemidesmosomal pro teins. In addition to autoantibodies, the cell-mediated immune reaction is considered to play an important part in blister formation. Objectives To investigate some T-cell activation markers and inflammatory c ytokines in the blister fluid and sera of patients with BP. Methods We measured soluble CD4 (sCD4) and soluble CD8 (sCD8), which have b een, respectively, associated with CD4 and CD8 T-cell activation. Enzyme-li nked immunosorbent assays were also used to quantify the production of the leucocyte chemoattractant interleukin (IL) -8 and of the cytokines IL-1 alp ha, IL-1 beta, IL-6, IL-10 and tumour necrosis factor-alpha, in the blister fluid and sera of 11 patients with BP. Results The mean +/- SD level of sCD4 in patients' blisters (42.4 +/- 25.0 units mL(-1)) was significantly elevated (P < 0.005) compared with that in their sera (11.2 +/- 8.9) and that in the suction blisters of 10 healthy pe ople (11.4 +/- 5.4; P < 0.005). Mean +/- SD IL-8 concentrations in BP blist ers (4683.6 +/- 3878.1 pg mL(-1)) were much higher than those in their sera (17.1 +/- 18.9; P < 0.001), and were very significantly elevated (P < 0.00 5) in comparison with those in suction blisters of healthy persons (512 +/- 292). sCD4 levels in BP blisters were inversely related to IL-10 levers (P = 0.03, r(2) = 0.85), IL-8 levels were positively related to sCD8 levels ( P = 0.01, r(2) = 0.54), and IL-1 beta levels were positively related to sCD 8 concentrations (P < 0.005, r(2) = 0.65). Conclusions The correlations suggest that there is a delicately orchestrate d network of cytokines and cell-mediated immunity operating in BP blisters.