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Semin Liver Dis 2021; 41(02): 150-162
DOI: 10.1055/s-0041-1723031
Review Article

Novel Mechanisms for Resolution of Liver Inflammation: Therapeutic Implications

Benedikt Kaufmann‡   *
1   Department of Pediatrics, University of California, San Diego (UCSD), California and Rady Children's Hospital, San Diego, California
2   Department of Surgery, TUM School of Medicine, Klinikum Rechts der Isar, Technical University of Munich, Munich, Germany
,
Agustina Reca‡   *
1   Department of Pediatrics, University of California, San Diego (UCSD), California and Rady Children's Hospital, San Diego, California
,
Andrea D. Kim
1   Department of Pediatrics, University of California, San Diego (UCSD), California and Rady Children's Hospital, San Diego, California
,
Ariel E. Feldstein
1   Department of Pediatrics, University of California, San Diego (UCSD), California and Rady Children's Hospital, San Diego, California
› Author Affiliations Funding This work was funded by NIH grants R01 DK113592, R01 AA024206 to A.E.F., German Research Foundation (DFG-Grant KA 5089/1–1) to B.K.
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Abstract

Traditional concepts have classically viewed resolution of inflammation as a passive process yet insight into the pathways by which inflammation is resolved has challenged this idea. Resolution has been revealed as a highly dynamic and active event that is essential to counteract the dysregulated inflammatory response that drives diverse disease states. Abrogation of the hepatic inflammatory response through the stimulation of proresolving mechanisms represents a new paradigm in the setting of chronic inflammatory-driven liver diseases. Elucidation of the role of different cells of the innate and adaptive immune system has highlighted the interplay between them as an important orchestrator of liver repair. A finely tuned interaction between neutrophils and macrophages has risen as revolutionary mechanism that drives the restoration of hepatic function and architecture. Specialized proresolving mediators have also been shown to act as stop signals of the inflammatory response and promote resolution as well as tissue regeneration. In this review, we discuss the discovery and understanding of the mechanisms by which inflammation is resolved and highlight novel proresolving pathways that represent promising therapeutic strategies.

Keywords

liver inflammation - resolution - immune system - macrophage - neutrophil - lipid mediators - novel therapy

* These authors contributed equally.




Publication History

Article published online:
24 March 2021

© 2021. Thieme. All rights reserved.

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