Figure 5

Tozorakimab can inhibit endogenous IL-33^red-driven inflammatory responses in vitro and in vivo. (a) Western blot of human IL-33 in lung tissue lysate derived from a healthy individual who was an ex-smoker (representative of n = 3). For the full western blot, please see Supplementary figure S4. (b) Inhibition of IL-8 release in HUVECs treated with human lung lysate (mean ± SD, n = 3). (c) Study to determine inhibition of endogenous IL-33-dependent IL-5 in BALF following an ALT challenge. Tozorakimab administered i.p. 24 h before ALT challenge. The study was performed in female humanized-IL-33 KI, mouse-IL-33 KO mice (huIL-33KI). (d) Inhibition of ALT driven IL-5 release in BALF. PBS, human-isotype mAb and mouse-isotype mAb controls were used (n = 6). A Browne–Forsyth ANOVA was used to test the impact of dose on log₁₀ transformed IL-5 levels to confirm that the samples were of similar variance. The post hoc Dunnett’s multiple comparison test was then used to generate p values (as stated) for the comparisons of interest (Prism 8). ALT, Alternaria alternata; ANOVA, analysis of variance; BALF, bronchoalveolar lavage fluid; ELISA, enzyme-linked immunosorbent assay; FL, full length; HUVEC, human umbilical vein endothelial cell; IL, interleukin; i.p., intraperitoneal; KI, knock in; KO, knockout; mAb, monoclonal antibody; PBS, phosphate buffered saline; red, reduced; SD, standard deviation; sST2, soluble serum stimulated 2.