Fig 2: The effect of anti-IL-1R7 antibody on LPS-induced cytokine production in human whole blood culture. Human whole blood cultures were pretreated with or without 5 µg/ml anti-IL-1R7 or 10 µg/ml IL-1Ra or 1 µg/ml IL-18BP for at least 30 min before they were stimulated with 10 ng/ml LPS for 3 days. A, effect of anti-IL-1R7 on LPS-induced IFN? in the whole blood culture. B, effect of anti-IL-1R7 on LPS-induced TNFa in the whole blood culture. C, effect of anti-IL-1R7 on LPS-induced IL-6 in the whole blood culture. Mean ± SD Percent change of LPS-induced cytokine production in human whole blood culture with various concentrations of anti-IL-1R7 or IL-18BP or IL-1Ra (n ? 5). ***p < 0.001, **p < 0.01, and *p < 0.05, compared with LPS alone.

Fig 3: Models depicting how IL-18BP and anti-IL-1R7 antibodies inhibit the IL-18 pathway.A, the model of how IL-18BP modulates the function of IL-18 or IL-37. B, the model of how anti-IL-1R7 regulates the function of IL-18 while leaving the IL-37 pathway intact. For simplicity, only the extracellular domains of the receptor complexes are shown.

Fig 4: The effect of anti-IL-1R7 antibody on IL-18-mediated proinflammatory signaling and cytokine production in different cell line cultures.A, inhibition of IL-18-induced gene reporter activation by anti-IL-1R7 MAB300 and MAB304 or the reference mAB MAB1181 in HEK-Blue IL-18 cells. SEAP (Secreted embryonic alkaline phosphatase) activity in the supernatant is determined as a measure of the activation of the IL-18 signaling pathway as described in Experimental procedures. B, inhibition of IL-18-induced IL-6 production by anti-IL-1R7 or the reference mAB in human A549-hIL-1R7/9 cells. C, inhibition of IL-18-induced IFN? release by anti-IL-1R7 or the reference mAB in human KG-1 cells. D, effect of anti-IL-1R7 on IL-18-induced IL-6 in human A549-hIL-1R7 cell cultures. Cells were pretreated with or without isotype control antibody (Ctrl), anti-IL-1R7 or IL-18BP for at least 30 min before they were stimulated with 50 ng/ml IL-18 for 24 h. Mean ± SD Percent change of IL-18-induced IL-6 production in A549-hIL-1R7 cells treated with various concentrations of anti-IL-1R7 or its isotype control or IL-18BP (n ?3 for all conditions). ***p < 0.001 compared with IL-18 alone.

Fig 5: The effect of anti-IL-1R7 antibody on LPS-induced cytokine production in human PBMC culture. Cells were pretreated with or without Ctrl, anti-IL-1R7, or IL-18BP or IL-1Ra for at least 30 min before they were stimulated with 10 ng/ml LPS for 24 h. A, effect of anti-IL-1R7 on LPS-induced IFN?. B Effect of anti-IL-1R7 on LPS-induced TNFa. C, effect of anti-IL-1R7 on LPS-induced IL-6. D, effect of anti-IL-1R7 on LPS-induced IL-1ß. Mean ± SD Percent change of LPS-induced cytokine production in PBMCs with various concentrations of anti-IL-1R7 or its isotype control or IL-18BP or IL-1Ra (n ?4 for all conditions). ***p < 0.001, **p < 0.01, and *p < 0.05, compared with LPS alone.