Resolution Pharmacology: State-of-the-art and therapeutic landscape

In 2015, we coined the term "Resolution Pharmacology" to indicate how the biology of the resolution of inflammation could, and should, be harnessed to produce novel therapeutics. Here we update these concepts and discuss the most recent developments in this innovative field of pharmacology. We begin by discussing how the inflammatory response is lifesaving through the engagement, expression, and function of several mediators, which have been labeled as proinflammatory or proresolving mediators. In reality, they act in concert and regulate each other in a fully integrated fashion, so that the notion between inflammation onset and inflammation resolution, as 2 distinct phases, is mainly didactic and temporal. Moreover, the observation that the inflammatory reaction that our body mounts always, or nearly always, resolves indicate that inflammation resolution is a robust process. What remain to be addressed, though, is how to harness the biology of acute resolving inflammation so that innovative therapeutic options can be offered for the clinical management of chronic nonresolving inflammation. The holistic view of physiological inflammation, and its disruption in pathology, comes with implications in relation to the application of Resolution Pharmacology. We predict resolution-based drugs will work better in presence of a florid inflammatory status, which would augment expression of resolution targets. We conclude by proposing a renovated focus on endogenous tissue-protective regenerative pathways by specific targets for drug development programs: Resolution Pharmacology remains an untapped opportunity for the pharmaceutical industry. SIGNIFICANCE STATEMENT: The process of the resolution of inflammation represents an integral part of the whole acute inflammatory response. A florid inflammatory reaction ensures proper engagement of resolution mechanisms. Dysregulation in resolution mechanisms can lead to disease. Conversely, harnessing resolution can offer therapeutic guidance to develop medicines that are disease independent, broadening their potential. There is ongoing intensive clinical development in this area. Proresolving drugs will be patient centric in their pharmacology and would promote natural processes of healing and repair.