HDAC inhibition increases mortality to nonsevere infection with K pneumonia and C albicans. BALB/c mice were injected intraperitoneally with valproate (Orfiril, 200 mg/kg) or phosphate-buffered saline (PBS). (A) Peritoneal exudate cells and splenocytes were collected after 1 hour. Histone H4 acetylation (AcH4) was analyzed by Western blotting. (B-C) Mice were infected intranasally with 10 CFU of K pneumoniae 15 minutes after valproate. (B) Circulating bacterial counts 3 days after infection and (C) survival (n = 15 mice per treatment groups; P = .04 and .0004 for bacterial counts and survival, respectively). The dashed line represents the lower limit of detection. (D) Survival of BALB/c mice injected with 1.2 × 105 CFU of C albicans and treated with valproate or PBS daily (n = 18 mice per treatment group; P = .02).
