A Novel therapeutic strategy targeting TIRAP-mediated signaling in sepsis

Abstract

Sepsis syndrome, its epidemiology, and causes: Sepsis is a critical clinical syndrome with life-threatening organ dysfunction induced by a dysregulated host response to infection. It is a life-threatening and expensive disease burden worldwide [1, 2]. Although sepsis has long been recognized, it was not clinically defined until the late 20th century due to the lack of sepsis patients surviving long enough to be studied or develop organ dysfunction sequelae. In the past 50 years, sepsis was being defined as the development of host systemic inflammatory response syndrome (SIRS) against microbial infection [3]. However, according to the Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3) held in 2016, sepsis is defined as “a life-threatening organ dysfunction originating due to the dysregulated host immune response to the infection” and septic shock as its subset, where the exaggerated and abnormal response in circulatory, cellular, and metabolic system are major factors for a greater risk of mortality among patients as compared to sepsis alone [1-3]. Sepsis is considered a major cause of health loss, but data for the global burden of sepsis are limited as the estimated figures are based upon data mainly collected from high-income countries, while data are scarce on its incidence in low- and middle-income countries. A recently compiled report on the global burden of sepsis (from 1990 to 2017) estimated about 48·9 million (95% uncertainty interval [UI] 38·9–62·9) incident cases of sepsis worldwide and 11·0 million (10·1–12·0) sepsis-related deaths representing 19·7% (18·2–21·4) of all global deaths in the year 2017 only [4-6]. As per the report, the 282 underlying causes of sepsis are broadly categorized into infections, injuries, and non-communicable diseases (NCDs) which account for the total sepsis in both sexes as depicted in Figure 1 [4].