Specialized pro-resolving mediators

Specialized pro-resolving mediators (SPM, also termed specialized proresolving mediators) are a large and growing class of cell signaling molecules formed in cells by the metabolism of polyunsaturated fatty acids (PUFA) by one or a combination of lipoxygenase, cyclooxygenase, and cytochrome P450 monooxygenase enzymes. Pre-clinical studies, primarily in animal models and human tissues, implicate SPM in orchestrating the resolution of inflammation.[1][2][3] Prominent members include the resolvins and protectins.

SPM join the long list of other physiological agents which tend to limit inflammation (see Inflammation § Resolution) including glucocorticoids, interleukin 10 (an anti-inflammatory cytokine), interleukin 1 receptor antagonist (an inhibitor of the action of pro-inflammatory cytokine, interleukin 1), annexin A1 (an inhibitor of formation of pro-inflammatory metabolites of polyunsaturated fatty acids, and the gaseous resolvins, carbon monoxide (see Carbon monoxide § Physiology), nitric oxide (see Nitric oxide § Biological functions), and hydrogen sulfide (see Hydrogen sulfide §§ Biosynthesis​ and Signalling role).[4][5]

The absolute as well as relative roles of the SPM along with other physiological anti-inflammatory agents in resolving human inflammatory responses remain to be defined precisely. However, studies suggest that synthetic SPM that are resistant to being metabolically inactivated hold promise of being clinically useful pharmacological tools for preventing and resolving a wide range of pathological inflammatory responses along with the tissue destruction and morbidity that these responses cause. Based on animal model studies, the inflammation-based diseases which may be treated by such metabolically resistant SPM analogs include not only pathological and tissue damaging responses to invading pathogens but also a wide array of pathological conditions in which inflammation is a contributing factor such as allergic inflammatory diseases (e.g. asthma, rhinitis), autoimmune diseases (e.g. rheumatoid arthritis, systemic lupus erythematosus), psoriasis, atherosclerosis disease leading to heart attacks and strokes, type 1 and type 2 diabetes, the metabolic syndrome, and certain dementia syndromes (e.g. Alzheimer's disease, Huntington's disease).[1][2][3]

Many of the SPM are metabolites of omega−3 fatty acids and have been proposed to be responsible for the anti-inflammatory actions that are attributed to omega−3 fatty acid-rich diets.[6]

  1. ^ a b Qu Q, Xuan W, Fan GH (2015). "Roles of resolvins in the resolution of acute inflammation". Cell Biology International. 39 (1): 3–22. doi:10.1002/cbin.10345. PMID 25052386. S2CID 10160642.
  2. ^ a b Serhan CN, Chiang N, Dalli J (2015). "The resolution code of acute inflammation: Novel pro-resolving lipid mediators in resolution". Seminars in Immunology. 27 (3): 200–15. doi:10.1016/j.smim.2015.03.004. PMC 4515371. PMID 25857211.
  3. ^ a b Heras-Sandoval D, Pedraza-Chaverri J, Pérez-Rojas JM (2016). "Role of docosahexaenoic acid in the modulation of glial cells in Alzheimer's disease". Journal of Neuroinflammation. 13 (1): 61. doi:10.1186/s12974-016-0525-7. PMC 4787218. PMID 26965310.
  4. ^ Haworth O, Buckley CD (2015). "Pathways involved in the resolution of inflammatory joint disease". Seminars in Immunology. 27 (3): 194–9. doi:10.1016/j.smim.2015.04.002. PMID 25944272.
  5. ^ Wallace JL, Ianaro A, Flannigan KL, Cirino G (2015). "Gaseous mediators in resolution of inflammation". Seminars in Immunology. 27 (3): 227–33. doi:10.1016/j.smim.2015.05.004. PMID 26095908.
  6. ^ Serhan CN (2014). "Pro-resolving lipid mediators are leads for resolution physiology". Nature. 510 (7503): 92–101. Bibcode:2014Natur.510...92S. doi:10.1038/nature13479. PMC 4263681. PMID 24899309.