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Resolution of inflammation: the beginning programs the end.

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

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Summary

Inflammation resolution involves an active program switching from prostaglandins to lipoxins, initiating neutrophil apoptosis and clearance by macrophages. This process, involving omega-3 fatty acids, promotes tissue repair and reduces inflammation.

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Area of Science:

  • Immunology
  • Biochemistry
  • Cell Biology

Background:

  • Mechanisms of acute inflammation resolution are not fully understood.
  • Inflammation resolution is an active, coordinated process, not merely passive decay.
  • Granulocytes play a key role in initiating the resolution phase.

Purpose of the Study:

  • To elucidate the molecular mechanisms underlying acute inflammation resolution.
  • To identify key mediators and cellular players involved in the termination of inflammatory responses.
  • To explore the role of omega-3 polyunsaturated fatty acids in inflammation resolution.

Main Methods:

  • Analysis of cellular signaling pathways during inflammation.
  • Investigation of lipid mediator biosynthesis (lipoxins, resolvins, protectins).
  • Study of neutrophil apoptosis and clearance by macrophages.

Main Results:

  • Lipoxins initiate the switch from inflammatory mediators, ceasing neutrophil recruitment.
  • Neutrophil apoptosis is induced by resolvins and protectins derived from omega-3 fatty acids.
  • Macrophage phagocytosis of apoptotic neutrophils leads to release of anti-inflammatory cytokines like TGF-β1.

Conclusions:

  • Inflammation resolution is an active, programmed process involving specific lipid mediators and cellular interactions.
  • Omega-3 fatty acid-derived mediators are crucial for timely resolution and preventing chronic inflammation.
  • Understanding these pathways may lead to novel therapeutic strategies for inflammatory diseases.