IR-61 treatment affords protection against sepsis. (a–c) Mice treated with IR-61 displayed higher survival during LPS sepsis, E. coli sepsis, and CLP sepsis (Vehicle vs IR-61: p = 0.0001 (LPS), p = 0.0230 (E. coli) and p = 0.0029 (CLP); n = 10 mice per group in LPS sepsis and CLP sepsis, n = 12 mice per group in E. coli sepsis). (d) The bacterial clearance in the blood, PLF, spleen, and lung was detected 24 h after IR-61 treatment in the CLP-induced sepsis mice (Vehicle vs IR-61: p = 0.0079 (blood), p = 0.0033 (PLF), p = 0.0387 (spleen), p = 0.0137 (lung); n = 4–5 mice per group). (e, f) Cytokine concentrations in plasma (e) (Vehicle vs IR-61: p = 0.0006 (Tnf), p = 0.0050 (IL-6), p = 0.0001 (IL-1β), p = 0.0012 (IL-10); n = 5 mice per group) and PLF (f) obtained from CLP-induced septic mice treated with IR-61 for 24 h (Vehicle vs IR-61: p = 0.0079 (Tnf), p = 0.0048 (IL-6), p = 0.0005 (IL-1β), p = 0.0217 (IL-10); n = 5 mice per group). (g) Measurements of plasma biochemical parameters for the liver, kidney, heart, and pancreas functions (Vehicle vs IR-61: p = 0.0079 (BUN), p = 0.0003 (ALT), p = 0.0011 (AST), p = 0.0026 (CK), p = 0.0002 (AMYL); n = 5 mice per group). (h) Histopathological analysis of the lung and kidney. Representative images are shown (bars represent 250 μm; n = 5 mice per group). Results are presented as the mean ± SD (∗p < 0.05, ∗∗p < 0.01, and ∗∗∗p < 0.001; Mantel–Cox log-rank test (longitudinal data in panels a–c); two-sided Student's t-test or Mann–Whitney test (graphs in panels d–g)).