The viability of using epigenetic drugs as a treatment of patients in sepsis - a translational perspective

Abstract

Sepsis is a serious and potentially lethal clinical condition characterized by dysregulated immune and systemic inflammatory responses (SIRS) to an infection. Although sepsis has a high mortality rate (reaching 25% in Europe and North America), the clinical interventions available are still limited. In the bottom of this exacerbation of the immune response, that evolves to immunosuppression and immune paralysis, lies epigenetic mechanisms. In sepsis, the balance between activated and repressed immune related genes is at lost, and to recover that epigenetic based drugs promises to be the future of sepsis treatment. Histone deacetylase inhibitors (HDAC’s inhibitors) are drugs based in the epigenetic mechanism of acetylation and deacetylation of histones, and they have already been tested - phases three and four of clinical trials - as treatment for other diseases, such as multiple myeloma, and cutaneous t-cell lymphoma. Furthermore, experimental studies in sepsis models shows that HDAC’s inhibitors are a promising suppressor of the exacerbated inflammatory response. Therefore, as the recent works shows, epigenetic drugs should be considered a viable sepsis therapy in the future. The focus of this review is to present the most recent scientific advances in the basic and clinical areas of epigenetic as a sepsis treatment, opening opportunities for the use of epigenetic in treating this condition.