Interleukin-18 Binding Protein in the Sera of Patients with Wegener's Granulomatosis

In the present study, we examined the levels of the pro-inflammatory cytokine IL-18 and its natural inhibitor, the IL-18 binding protein (IL-18BP), in sera of Wegener's granulomatosis (WG) patients at various stages of the disease. Sera from eight consecutive biopsy-proven systemic WG patients (four men and four women; age at diagnosis 58.4 +/- 13.8 years) were obtained longitudinally with a follow-up period of 55.2 +/- 30 months. Sera obtained from 50 healthy subjects were used as controls. Serum levels of IL-18, IL-18BP, and free IL-18 obtained during an active phase of the disease (Birmingham Vasculitis Activity Score, BVAS > 10) were more than twofold higher than levels in the same patients during inactive disease stages (BVAS < 5; P < 0.002; P < 0.006, and P < 0.03 for IL-18, IL-18BP, and free IL-18, respectively). During inactive stages, the levels of these markers were comparable to those of healthy controls. The elevated levels of IL-18 and IL-18BP in sera during active stages of disease suggest a possible role in the pathogenesis and course of the WG. Despite the elevated IL-18BP levels during active disease, free IL-18 remained higher than in the inactive disease stages, suggesting a potential benefit of administration of exogenous IL-18BP as a novel therapeutic approach for active WG.