HDAC inhibition protects from lethal toxic shock and severe sepsis. (A-B) BALB/c mice were injected intraperitoneally with valproate (Orfiril, 200 mg/kg started 2 days before and discontinued 2 days after induction of shock) or PBS. Animals were sensitized with D-galactosamine and injected intraperitoneally with Pam₃CSK₄. (A) Plasma levels of IL-6 and IL-12p40 were determined 1 hour and 3 hours after challenge with Pam₃CSK₄. Data are mean ± SD of 8 mice per treatment group. *P < .001 for valproate versus PBS. (B) Survival of BALB/c mice subjected to Pam₃CSK₄-induced shock (n = 11 mice per treatment group; P = .001). (C) Survival of BALB/c mice subjected to CLP and treated with either valproate or PBS (every 12 hours, starting 30 minutes after surgery; n = 16-18 mice per treatment group). P = .04.