Figure 2. IL-17A inhibition and loss of IL-17 receptor C protect mice against LPS-induced increased lung permeability.

(a) Anti-IL17A antibody or control IgG was administered intravenously 2 days after endotracheal administration of H₂O or LPS (100 μg/mouse) to C57Bl/6 wild type mice. Permeability was measured by leakage of Evan’s blue-labeled intravascular albumin into the lung at 4 days after LPS or H₂O administration. Data reported as mean ± SEM, n=10 in LPS groups and n=5 in H₂O groups. *p<0.05 by one-way ANOVA and Tukey-Kramer test. (b) LPS or H₂O was administered to control or IL-17 receptor C knock-out (IL-17RC KO) mice and permeability was assessed at 4 days, as in figure 2a. Data reported as mean ± SEM, n=9 in LPS groups and n=3 in H₂O groups. *p<0.05 by one-way ANOVA and Tukey-Kramer test. (c) Higher dose LPS (125 μg per mouse) was administered endotracheally to control or IL-17 receptor C knockout mice and survival was assessed over the next 10 days. Data reported as percent survival, n=35 in each group. **p<0.01 by log-rank Mantel-Cox test. (d) Body weight was measured daily in all surviving high-dose LPS-treated control and IL-17 receptor C knockout mice for 10 days. Data reported as percent weight change from initial weight. *p<0.05, **p<0.01, ***p<0.001 by one-way ANOVA and Bonferroni multiple comparison test. Confluent rat type II alveolar epithelial monolayers were cultured on collagen-impregnated semi-permeable membrane inserts in the presence of serum-free media with and without recombinant rat IL-17A for 24 hours. (e) Transepithelial electrical resistance and (f) permeability to FITC-dextran were measured. Data reported as mean ± SEM, n=6 per group. **p<0.01,***p<0.001 by student t-test.