Fig. 2

Effect of peptidomimetic fluoromethylketones on survival of mice following LPS challenge. Mice were injected ip with 500 µg (A-C) or 200 µg (D) of LPS at time 0. (A-D) Treatments at times indicated by arrows: (□), vehicle 2 (see Materials and Methods); (◯), IDN 1529 (10 mg/kg per injection in vehicle 2); (△), IDN 1965 (10 mg/kg per injection in vehicle 2). Asterisks denote statistically significant differences for outcome of treatment with IDN 1529 compared to treatment with vehicle (A, p < 0.01; B, p < 0.01; C, p < 0.01, D, p < 0.01). In no case was there a statistically significant difference between outcomes for mice treated with IDN 1965 or with vehicle. (A) Treatment with peptidomimetic fluoromethylketones started 0.5 hr before LPS. Results are pooled for the following numbers of mice in four independent experiments: (□), 25; (◯), 20; (△), 10. (B) Treatment with peptidomimetic fluoromethylketones started 1 hr after LPS. Results are pooled for the following numbers of mice in three independent experiments: (□), 15; (◯), 15; (△), 10. (C) Treatment with peptidomimetic fluoromethylketones started 3 hr after LPS. Results are pooled for the following numbers of mice in two independent experiments: (□), 10; (◯), 10. (D) Treatment with peptidomimetic fluoromethylketones started 1 hr after LPS. Results are pooled for the following numbers of mice in three independent experiments: (□), 17; (◯), 17; (△) 17.