Structural elucidation and physiologic functions of specialized pro-resolving mediators and their receptors.
The acute inflammatory response is host-protective to contain foreign invaders. Many of today's pharmacopeia that block pro-inflammatory chemical mediators can cause serious unwanted side effects such as immune suppression. Uncontrolled inflammation is now considered a pathophysiologic basis associated with many widely occurring diseases such as cardiovascular disease, neurodegenerative diseases, diabetes, obesity and asthma, as well as the classic inflammatory diseases, e.g. arthritis, periodontal diseases. The inflammatory response is designated to be a self-limited process that produces a superfamily of chemical mediators that stimulate resolution of inflammatory responses. Specialized proresolving mediators (SPM) uncovered in recent years are endogenous mediators that include omega-3-derived families resolvins, protectins and maresins, as well as arachidonic acid-derived (n-6) lipoxins that stimulate and promote resolution of inflammation, clearance of microbes, reduce pain and promote tissue regeneration via novel mechanisms. Here, we review recent evidence from human and preclinical animal studies, together with the structural and functional elucidation of SPM indicating the SPM as physiologic mediators and pharmacologic agonists that stimulate resolution of inflammation and infection. These results suggest that it is time to develop immunoresolvents as agonists for testing resolution pharmacology in nutrition and health as well as in human diseases and during surgery.
Center for Experimental Therapeutics and Reperfusion Injury, Department of Anesthesiology, Perioperative and Pain Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, United States.
Nan
N
Chiang
Center for Experimental Therapeutics and Reperfusion Injury, Department of Anesthesiology, Perioperative and Pain Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, United States. Electronic address: cserhan@bwh.harvard.edu.
Charles N
CN
Serhan
D000818:Animals; D002986:Clinical Trials as Topic; D004195:Disease Models, Animal; D015525:Fatty Acids, Omega-3 / Q000378:metabolism; D054884:Host-Pathogen Interactions; D006801:Humans; D007239:Infections / Q000188:drug therapy / Q000209:etiology / Q000378:metabolism; D007249:Inflammation / Q000209:etiology* / Q000378:metabolism* / Q000473:pathology / Q000628:therapy; D018836:Inflammation Mediators / Q000737:chemistry* / Q000502:physiology* / Q000627:therapeutic use; D050356:Lipid Metabolism; D012038:Regeneration; D015398:Signal Transduction; D013329:Structure-Activity Relationship; D016896:Treatment Outcome
D015525:Fatty Acids, Omega-3; D018836:Inflammation Mediators
Inflammation; Leukocytes; Omega-3 PUFA; Resolvins; maresins; protectins