Potential therapeutic application of epigenetic mechanisms involved in the septic pathology

Epigenetic programming, dynamically regulated by histone acetylation, may play a key role in the pathophysiology of sepsis. Mice with cecal ligation and puncture (CLP)-induced polymicrobial sepsis were used to examine whether histone deacetylase (HDAC) can contribute to sepsis-associated inflammation and apoptosis. Histone H3 and H4 acetylation levels were increased, and HDAC1, HDAC2, and HDAC3 protein levels were decreased in lungs after CLP. The results with HDAC inhibitors indicated that they are a unique agent to prevent cell apoptosis in sepsis at their doses that do not improve inflammatory features. This study also represents the down-regulation of HDACs in sepsis, but suggest that imbalance in histone acetylation may play a contributory role in expression or repression of genes involved in septic cell apoptosis.