Figure 2. Epirubicin promotes disease tolerance to severe sepsis.

(a) Polymicrobial load (CFUs) in blood, lung, liver, kidney and spleen, at indicated time points, of C57BL/6 animals undergoing CLP and treated with PBS (C+P) or epirubicin (C+E) (0.6μg/g body weight) at the time of procedure and 24 hours later. Each circle represents individual animals. Horizontal lines indicate arithmetic means ± SEM. (b) and (c) Epirubicin counteracts tissue damage and inflammation associated with CLP as assessed by (b) LDH, CK, ALT, urea and (c) TNF, IL-1β, IL-6 and HMGB1 plasma concentrations in C57BL/6 wild-type animals 24 hours after mock CLP (S) (n=2) or CLP followed by treatment with PBS (C+P) (n=5) or epirubicin (C+E) (n=7) as in (a). Results shown represent arithmetic means ± SEM from duplicate (b) or triplicate (c) readings per animal. (d) Survival of C57BL/6 wild-type animals following lethal LPS injection and treatment with carrier (PBS) or epirubicin (Epi) as in (a). (e) Survival of C57BL/6 wild-type animals subjected to CLP treated with carrier (PBS), meropenem (40μg/g body weight/day) or epirubicin (Epi) as in (a). (f) CFUs in blood, at indicated time, of C57BL/6 animals undergoing mock CLP (S) or CLP followed by treatement with PBS (C+P), epirubicin (C+E) or meropenem (C+M) as in (a). Each circle represents individual animals. Horizontal lines indicate arithmetic means ± SEM. (g) IL-1β, TNF and HMGB1 plasma concentrations in C57BL/6 wild-type animals 24 hours after CLP followed by treatment with PBS (C+P) (n=4), epirubicin (C+E) (n=5) or meropenem (C+M) (n=5) as in (c). ns, not significant; *P<0.05; **P<0.01; ***P<0.001 (log-rank (Mantel-Cox) test for (d) and (e), Mann-Whitney test for (a) and (f), and unpaired t test for (b), (c) and (g)). See also Figure S2.