Figure 4: Pharmacological inhibition of HDAC6 protects mice from LPS-induced acute inflammation.

(a–d) TBSA treatment modified LPS-triggered production of IL-10, TNF-alpha, IL-6 and IL-1beta in vivo. Male C57BL/6 mice were injected with either TBSA (0.5 mg per kg) or vehicle DMSO by daily i.p. for 7 days, followed by i.p. injection of LPS (50 μg per mouse) or vehicle PBS (five mice per group). After 4 h, serum samples were harvested and cytokine concentrations were measured by ELISA. LPS-induced IL-10 levels in serum were markedly increased in TBSA-injected mice, compared with DMSO vehicle injection (a). LPS-triggered TNF-alpha (b), IL-6 (c) and IL-1beta (d) levels in serum were decreased in TBSA-injected mice, compared with DMSO-injected mice. The graph shows the means with s.e.m. (error bars). Asterisks indicate statistical significance (*P<0.05 and **P<0.01, Student’s t-test). (e) Mice were injected with TBSA (0.5 mg per kg) or vehicle DMSO by daily i.p. for 7 days followed by PBS or LPS (5 mg per kg) i.p. injection once. For the first 10 h post LPS challenge, survival was checked every 2 h. Afterwards, the survival was checked every 10 h. Survival curves showed a significant difference between DMSO and TBSA-treated mice (log-rank analysis P<0.01; n=10 in each group).