Sepsis Immunometabolism: From Defining Sepsis to Understanding How Energy Production Affects Immune Response

Objectives: This review will examine current definitions and trends in sepsis management as well pathophysiologic mechanisms in animal and ex vivo studies that correlate decreased energy production with deranged inflammatory response during the septic process. Data Sources: The latest articles in the literature that focus on the role of immunometabolism and associated mechanisms in sepsis were selected. Study Selection: The most relevant, original articles were included in the review. Data Extraction: All pertinent data for sepsis definitions as well as changes in immunometabolic pathways during the septic process was reviewed and assessed for inclusion in this article. Data Synthesis: Sepsis is a major cause of multiple organ dysfunction. It is the principal cause of death resulting from infection and one of the most expensive conditions treated in the United States. Despite current efforts to accurately define sepsis, novel treatments and highly trained providers, mortality rates for sepsis remain high, prompting a need for further investigation of underlying immunometabolic mechanisms to identify potential treatment targets. The definition of sepsis has shifted and changed in the past few decades due to poorly defined criteria, as well as unclear guidelines for providers with regards to management of severe sepsis and septic shock. The early identification of patients with a systemic inflammatory response that will progress to septic shock is critical since recent traditional therapeutic approaches, such as early goal-directed therapy, IV immunoglobulin, and anti–tumor necrosis factor-α antibodies have failed. Conclusions: There are no effective anti-sepsis drug therapies due to complex inflammatory and metabolic interactions. Further studies regarding the interface between innate immunity and metabolism should be investigated to effectively address septic patient mortality rates.