Systemic juvenile idiopathic arthritis or adult-onset Still's disease are also characterized by high serum IL-18 concentrations and are treated by IL-18BP.
This is the first clinical study to determine if interleukin (IL)-18 inhibition, using the recombinant human IL-18 binding protein, tadekinig alfa, is a therapeutic option in AOSD.
PBMCs from ten patients with AOSD were stimulated with recombinant human IL-37 protein, and expression levels of tumor necrosis factor (TNF)-α, IL-6, IL-10, IL-1β, and IL-18 were determined by qRT-PCR and ELISA.
IMQ (an effective Toll-like receptor 7 ligand; 10 <i>µ</i>g/ml and 25 <i>µ</i>g/ml) stimulation of PBMC from patients with AOSD induced dose-dependent increases of mRNA expression of NLRP3 (mean ± standard error of the mean, 2.06 ± 0.46 and 6.05 ± 1.84, respectively), caspase-1 (1.81 ± 0.23 and 4.25 ± 0.48), IL-1β (5.68 ± 1.51 and 12.13 ± 3.71), and IL-18 (2.32 ± 0.37 and 4.81 ± 0.51) compared with controls (all p < 0.005).
Upregulation of circulating miR-134 was associated with elevated IL-18 levels by targeting IL-18BP in AOSD patients and was positively correlated with disease activity, suggesting its involvement in AOSD pathogenesis.
IL-18 and IL-1β, two proinflammatory cytokines processed through the inflammasome machinery, are key factors in the pathogenesis of AOSD; they cause IL-6 and Th1 cytokine secretion as well as NK cell dysregulation leading to macrophage activation.
Significantly lower IL-18 levels were demonstrated in AOSD patients with a monocyclic systemic course than in those with a polycyclic systemic course or a chronic articular course.
Increased apoptosis of peripheral blood lymphocytes and its association with interleukin-18 in patients with active untreated adult-onset Still's disease.
Recently, we reported that genetic polymorphisms within the human IL18 gene were associated with disease susceptibility to adult-onset Still's disease (AOSD), which is characterized by extraordinarily high serum levels of IL-18.
Recently, IL-18 promoter polymorphisms were characterized as risk factors for inflammatory diseases such as sepsis, asthma and adult-onset Still's disease.
Percentages of IFNgamma-producing Th cells and Th1/Th2 ratio in PB correlated significantly with clinical activity score and serum IL18 levels in patients with AOSD.
The aim of the present study was to screen for genetic polymorphisms in the human IL-18 (hIL-18) gene and to determine the association of polymorphisms with susceptibility to AOSD.