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Resolution of inflammation: the beginning programs the end

Nature Immunology volume 6, pages 1191–1197 (2005)Cite this article

Abstract

Acute inflammation normally resolves by mechanisms that have remained somewhat elusive. Emerging evidence now suggests that an active, coordinated program of resolution initiates in the first few hours after an inflammatory response begins. After entering tissues, granulocytes promote the switch of arachidonic acid–derived prostaglandins and leukotrienes to lipoxins, which initiate the termination sequence. Neutrophil recruitment thus ceases and programmed death by apoptosis is engaged. These events coincide with the biosynthesis, from omega-3 polyunsaturated fatty acids, of resolvins and protectins, which critically shorten the period of neutrophil infiltration by initiating apoptosis. Consequently, apoptotic neutrophils undergo phagocytosis by macrophages, leading to neutrophil clearance and release of anti-inflammatory and reparative cytokines such as transforming growth factor-β1. The anti-inflammatory program ends with the departure of macrophages through the lymphatics. Understanding these and further details of the mechanism required for inflammation resolution may underpin the development of drugs that can resolve inflammatory processes in directed and controlled ways.

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Figure 1: Temporal events and programming in resolution of acute inflammation: the function of lipid-derived mediators.
Figure 2: Function of essential polyunsaturated fatty acids in the production of families of bioactive lipid mediators.
Figure 3: Regulation of macrophage activation by interaction with apoptotic cells.

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Acknowledgements

We thank M.H. Small, C. Gilchrist and C. Law for assistance in manuscript preparation, and K. Gotlinger for assistance with the illustrations. Supported by the National Institutes of Health (P50-DE016191 and GM38765 to C.N.S.), the Wellcome Trust (064487 to J.S.) and the Medical Research Council (J.S.).

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  1. Department of Anesthesiology, Center for Experimental Therapeutics and Reperfusion Injury, Perioperative, and Pain Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, 02115, Massachusetts, USA

    Charles N Serhan

  2. Medical Research Council Centre for Inflammation Research, University of Edinburgh, The Queen's Medical Research Institute, Edinburgh, EH16 4TJ, UK

    John Savill

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Correspondence to Charles N Serhan.

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Serhan, C., Savill, J. Resolution of inflammation: the beginning programs the end. Nat Immunol 6, 1191–1197 (2005). https://doi.org/10.1038/ni1276

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