Introduction: Microbial infections and resultant sepsis are leading causes of death in hospitals, representing approximately 20% of total deaths worldwide. Despite the difficulties in translating experimental insights into effective therapies for often heterogenous patient populations, an improved understanding of the pathogenic mechanisms underlying experimental sepsis is still urgently needed. Sepsis is partly attributable to dysregulated innate immune responses manifested by hyperinflammation and immunosuppression at different stages of microbial infections.
Areas covered: Here we review our recent progress in searching for late-acting mediators of experimental sepsis and propose high mobility group box 1 (HMGB1) and procathepsin-L (pCTS-L) as potential therapeutic targets for improving outcomes of lethal sepsis and other infectious diseases.
Expert opinion: It will be important to evaluate the efficacy of HMGB1- or pCTS-L-targeting agents for the clinical management of human sepsis and other infectious diseases in future studies.
Keywords: HMGB1; Innate immune cells; Late-acting mediator; Pyroptosis; Sepsis; hyperinflammation; pCTS-L.