Epilogue: The Well-Dosed Work of DAMPs in Their Commission to Restore and Maintain Homeostasis

Abstract

Part IV ends with a synopsis of some relevant new scientific knowledge on DAMPs that has emerged since the danger/injury model was formulated 24 years ago. A striking element of modern notion is that DAMPs are not only the key molecules to establish sterile inflammation upon sterile insults but also to promote, in close cooperation with MAMPs, infectious inflammation upon pathogen-mediated injury. Another valuable insight into their commission as gatekeepers of homeostasis refers to their well-dosed and correctly graduated emission according to and depending on the nature and intensity of the cell stress and/or tissue injury concerned. This feature is a mandatory prerequisite of DAMPs in (1) triggering efficient innate immune inflammatory responses, (2) instructing specific adaptive immune pathways, (3) promoting—as suppressing DAMPs—inflammation-resolving processes, and (4) orchestrating finally tissue-repairing mechanisms. To adapt to dangerous situations ranging from mild insults up to life-threatening injuries, the innate immune system works with tailor-made hierarchically ordered DAMPs in the form of a “DAMP axis” to meet the needs in every individual situation. It is in this sense that DAMPs can be regarded as unique molecules determining all scenarios of human life ranging from cell death to cell repair up to survival and new life.