In 2012, Nature Reviews Immunology organized a conference that brought together scientists and clinicians from both academia and industry to discuss one of the most pressing questions in medicine — how do we turn off rampant, undesirable inflammation? There is a growing appreciation that, similarly to the initiation of inflammation, the resolution of inflammation is an intricate and active process. Can we therefore harness the mediators involved in resolution responses to treat patients with chronic inflammatory or autoimmune diseases? Here, we ask five of the speakers from the conference to share their thoughts on this emerging field.
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Charles N. Serhan is an inventor on patents (for lipoxins and resolvins) assigned to Brigham and Women's Hospital and licensed to Resolvyx Pharmaceuticals. He is a scientific founder of Resolvyx Pharmaceuticals and owns equity in the company. His interests were reviewed and are managed by the Brigham and Women's Hospital and Partners HealthCare in accordance with their conflict of interest policies.
Paul P. Tak is an employee of GlaxoSmithKline.
The other authors declare no competing financial interests.
- Cholinergic anti-inflammatory pathway
A mechanism for neural inhibition of local and systemic inflammation that is controlled by vagus nerve stimulation.
The process by which dead or dying cells are removed through engulfment by phagocytes.
(Also known as icosanoids). A general term used to denote bioactive lipid mediators that contain 20 carbon atoms and are synthesized from arachidonic acid (a fatty acid present in membrane phospholipids) by the initial activities of either cyclooxygenases or lipoxygenases. Examples include prostaglandins, leukotrienes and lipoxins. Eicosanoids signal through G protein-coupled receptors and have important roles in inflammation, but also in many other biological processes, including reproduction and haemostasis.
The region at the junction between tendon and bone. This is a key site of pathology in spondyloarthritic diseases, such as ankylosing spondylitis.
Biological fluids that filter from the circulatory system into lesions or areas of inflammation. Exudate is characterized by a high content of plasma proteins, cells and cellular debris. Pus is an example of an exudate found in infected wounds and it contains bacteria and high concentrations of white blood cells.
A term that denotes agents that stimulate the resolution of inflammation. Examples include lipoxins, resolvins and protectins.
- Innate lymphoid cells
Lymphoid cells that do not express unique antigen receptors derived from gene rearrangement or cell-surface markers that are characteristic of other immune cell lineages. However, in response to innate tissue-derived signals, they secrete cytokines that are associated with T helper cell subsets. They can promote protective immunity during infection, but may also have pathological roles in certain diseases.
A class of eicosanoids derived from arachidonic acid by the action of arachidonate 5-lipoxygenase and downstream enzymes. They have a conjugated triene double-bond structure and various pro-inflammatory activities, including leukocyte activation (in the case of leukotriene B4) and bronchoconstriction (in the case of leukotriene C4 and leukotriene D4).
A class of eicosanoids that are produced by lipoxygenase-mediated metabolism of arachidonic acid. They are trihydroxytetraene-containing structures with potent biological activities in the resolution of inflammation.
- NADPH oxidase
NADPH oxidases are plasma membrane- and phagosomal membrane-bound enzyme complexes that transfer electrons from NADPH to molecular oxygen, promoting the generation of the reactive oxygen species superoxide.
- Positional memory
The basis by which cells know their spatial relationship to each other (in terms of top or bottom, left or right and inside or outside) is defined during embryological development. This relative 'positioning' of one cell to another is generally 'remembered' throughout life. However, during tissue pathology (for example, in cancer and during inflammation) positional memory can be lost.
Cyclopentane-ring-containing lipids derived from the metabolism of arachidonic acid by the action of cyclooxygenases and downstream synthase enzymes. They have a diverse range of biological activities and a well-recognized role in inflammation and pain.
A family of docosahexaenoic acid-derived mediators characterized by the presence of a conjugated triene double-bond structure and 22 carbons with 6 double bonds.
Lipid mediators that are induced in the resolution phase following acute inflammation. They are biosynthesized from the essential omega-3 fatty acids eicosapentaenoic acid and docosahexaenoic acid.
- Type 1 hypersensitivity responses
Immediate allergic reactions to allergens in previously sensitized individuals. These responses are mediated by pre-existing allergen-specific IgE antibodies, which promote the activation and degranulation of tissue mast cells and basophils in the blood.
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Buckley, C., Gilroy, D., Serhan, C. et al. The resolution of inflammation. Nat Rev Immunol 13, 59–66 (2013). https://doi.org/10.1038/nri3362
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