Development of Anti-inflammatory Drugs with Novel Mechanisms of Action Targeting Pyroptosis

Abstract

Programmed cell death plays various physiological roles, one of which is an immune response that protects the body from infectious pathogens such as bacteria and viruses. Pathogen infection causes dysfunction of cellular organelles, such as mitochondria and lysosomes, triggering stress signals that induce programmed cell death. In some cases, cell death coincides with intracellular inflammatory cytokine release. Such programmed cell death, accompanied by the induction of inflammatory responses, is called pyroptosis, which inhibits pathogen proliferation within cells and attracts leukocytes that eliminate the pathogens, thereby preventing infection spread. Additionally, pyroptosis can be induced by noninfectious stimuli such as drugs, pollutants, and nutrients, resulting in severe inflammatory disease. Therefore, the development of effective anti-inflammatory drugs that prevent pyroptosis based on the understanding of the mechanisms responsible for its induction is an urgent requirement. This review provides an overview of the non-infectious inflammatory response caused by pyroptosis and the development of new anti-inflammatory drugs that target organelles to prevent pyroptosis to treat relevant inflammatory diseases.