Mediators of the Resolution of the Inflammatory Response

• Published in: Trends in immunology Vol. 40; no. 3; pp. 212 - 227
• Main Authors: Sugimoto, Michelle A., Vago, Juliana P., Perretti, Mauro, Teixeira, Mauro M.
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 01-03-2019; Elsevier Limited
• Subjects: Animals; Anti-Inflammatory Agents - metabolism; Autoimmune Diseases - immunology; Cytokines; Cytokines - metabolism; Granulocytes; Homeostasis; Humans; Inflammation; Inflammation - immunology; Inflammation Mediators - metabolism; Inflammatory diseases; Inflammatory response; Lipids; Mice; Neutrophils; Peptides; Phagocytosis; Pharmacology; Proteins; Receptors
• DOI: 10.1016/j.it.2019.01.007
• EISSN: 1471-4981
• ISSN: 1471-4906

The termination of inflammation is governed by endogenous molecules collectively referred to as ‘mediators of resolution’ of inflammation. There is now strong evidence to suggest that failed resolution may underpin autoimmune and inflammatory diseases and could thus be targeted to decrease inflammation. There are many molecules that have been described as mediators of resolution, and new players are still being continuously discovered. To support the emerging field of ‘resolution pharmacology’, here we discuss the scientific strategies required to qualify a molecule as a resolution mediator. Systematic definition of the players of resolution, their receptors, and downstream mechanisms remains a necessary knowledge to move the field forward and suggest new targets for the development of novel therapies to treat inflammatory diseases.
A successful inflammatory response tends to resolve in a coordinated series of molecular and cellular events, including the resolving phase of inflammation. Exciting new discoveries have revealed a post-resolution phase of inflammation, composed of a third wave of leukocyte influx that seemingly links innate and adaptive immune systems.
Recent discoveries have suggested that failed or impaired resolution of inflammation may underpin the pathogenesis of certain chronic inflammatory diseases, such as inflammatory bowel disease and rheumatoid arthritis.
The identification of failed resolution as an underlying cause or contributing factor to certain human inflammatory diseases has brought new exciting therapeutic opportunities for treating inflammation, based on promoting events associated with resolution, rather than simply blocking proinflammatory pathways.
Recently, the potential of human translation is reflected by the identification/quantification of proresolving molecules and pathways in humans, and by the pioneering use of human models of inflammation to test the efficacy of proresolving agonists.
In order to effectively translate the knowledge of resolution biology into potential new therapeutics for a variety of inflammation-associated diseases, precise definitions of the cellular players, molecular mediators, receptors, and signaling pathways engaged during inflammation resolution are necessary.