Review Article | Published:

Specialized pro-resolving mediators: endogenous regulators of infection and inflammation

Nature Reviews Immunology volume 16, pages 5167 (2016) | Download Citation

Abstract

Specialized pro-resolving mediators (SPMs) are enzymatically derived from essential fatty acids and have important roles in orchestrating the resolution of tissue inflammation — that is, catabasis. Host responses to tissue infection elicit acute inflammation in an attempt to control invading pathogens. SPMs are lipid mediators that are part of a larger family of pro-resolving molecules, which includes proteins and gases, that together restrain inflammation and resolve the infection. These immunoresolvents are distinct from immunosuppressive molecules as they not only dampen inflammation but also promote host defence. Here, we focus primarily on SPMs and their roles in lung infection and inflammation to illustrate the potent actions these mediators play in restoring tissue homeostasis after an infection.

Key points

  • The immune response comprises not only pro-inflammatory and anti-inflammatory pathways but also pro-resolution mechanisms that serve to balance the need of the host to target microbial pathogens while preventing excess inflammation and bystander tissue damage.

  • Specialized pro-resolving mediators (SPMs) are enzymatically derived from essential fatty acids to serve as a novel class of immunoresolvents that limit acute responses and orchestrate the clearance of tissue pathogens, dying cells and debris from the battlefield of infectious inflammation.

  • SPMs are composed of lipoxins, E-series and D-series resolvins, protectins and maresins. Individual members of the SPM family serve as agonists at cognate receptors to induce cell-type specific responses.

  • Important regulatory roles for SPMs have been uncovered in host responses to several microorganisms, including bacterial, viral, fungal and parasitic pathogens.

  • SPMs also promote the resolution of non-infectious inflammation and tissue injury. Defects in host SPM pathways contribute to the development of chronic inflammatory diseases.

  • With the capacity to enhance host defence and modulate inflammation, SPMs represent a promising translational approach to enlist host resolution programmes for the treatment of infection and excess inflammation.

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Acknowledgements

he authors wish to acknowledge C. N. Serhan for his helpful advice in the preparation of this manuscript. This work was funded in part by US National Institutes of Health grants HL122531, U10HL109172, U01HL108712 and P01GM095467.

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Affiliations

  1. Department of Internal Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts 02115, USA.

    • Maria C. Basil
    •  & Bruce D. Levy

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  2. Search for Bruce D. Levy in:

Competing interests

B.D.L. is a co-inventor on patents assigned to Brigham and Women's Hospital; some of these patents (those pertaining to resolvins) are licensed to Resolvyx Pharmaceuticals. The interests of B.D.L. were reviewed and are managed by the Brigham and Women's Hospital and Partners HealthCare in accordance with their conflict-of-interest policies.

Corresponding author

Correspondence to Bruce D. Levy.

Glossary

Catabasis

An active process at the cellular and tissue level governed by specific mediators that promote a return to tissue homeostasis.

Efferocytosis

The cellular process by which phagocytes engulf dying and dead cells (for example, apoptotic or necrotic) for removal from tissues. It is part of the resolution programme to restore tissue homeostasis.

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https://doi.org/10.1038/nri.2015.4

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