Figure 7.
Modified SERPINs protect against inflammation in acute and chronic in vivo models of bradykinin-mediated pathology. (A) Carrageenan-induced paw swelling. Mice (n = 12 per group) were pretreated by IV injection (8 mg/kg α1AT variant, 16 mg/kg rC1INH, 1 mg/kg icatibant (HOE140) or 5 mg/kg Indomethacin). Hereafter (T = 0), mice were challenged by carrageenan injection into the dorsal side of the left hind paw. Changes in paw size were measured in triplicate before and during the carrageenan challenge. Data represent the mean ± SD. (B) DSS-induced colitis. On day 0 and 3, mice (n = 6 per group) received an IV injection with inhibitor (8 mg/kg α1AT variant, 16 mg/kg rC1INH). Hereafter (T = 0), mice were challenged with DSS (3% wt/vol) via their drinking water. The control group (baseline) received no DSS. After 6 days, mice underwent a gavage with FITC-dextran to determine epithelial leakage of the gut. Four hours after the gavage, mice were euthanized and FITC-DXS plasma levels were determined. Data are represented as box and whiskers plot (5% to 95% percentile). #P < .005, compared with vehicle by 1-way ANOVA with post-hoc Dunnett’s multiple comparison test.