Cited by 229Fatty Acid Research and HealthPhagocytosis and Immune RegulationImmune Response and Inflammation

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Is Resolution the End of Inflammation?

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Feehan, Karen T., Gilroy, Derek W.·2019·Trends in Molecular Medicine

DOI 10.1016/j.molmed.2019.01.006

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Abstract

Deciphering the origins of chronic inflammatory and autoimmune diseases remains elusive with reliance on therapies aimed at halting inflammation in its tracks. In recent years, an appreciation of targeting pathways by which inflammation is resolved has begun to rouse interest. Resolution of inflammation is driven by a complex set of mediators that regulate cellular events required to clear inflammatory cells from sites of infection or injury to restore tissue function. However, recent studies suggest that resolution is not the end of innate mediated immune responses to infection/injury. There is further immunological activity occurring after the resolution cascade is complete that alters the immune physiology of tissues, redefining what was once termed restorative homeostasis as adapted homeostasis.

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Li, H., Ruan, J., Huang, J., Yang, D., Yu, H., Wu, Y. C., Zhang, Y., & Wang, T. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms242417538 · Cited by 28
Role of Tristetraprolin in the Resolution of Inflammation
Rappl, P., Brüne, B., & Schmid, T. (2021) · Biology · doi:10.3390/biology10010066 · Cited by 26
“In fact, successful resolution is not the end of this dynamic process, but recent reports indicate that it is followed by a prolonged post-resolution phase characterized by an altered, immune suppressive environment [28,29].”
Background
Lycium barbarum polysaccharides ameliorate LPS‐induced inflammation of RAW264.7 cells and modify the behavioral score of peritonitis mice
Liu, Z., Yu, W., Zhou, H., Lan, Z., Wu, T., Xiong, S., Yan, L., & Liu, H. (2021) · Journal of Food Biochemistry · doi:10.1111/jfbc.13889 · Cited by 27
Inflamed synovial fluid induces a homeostatic response in bone marrow mononuclear cells in vitro: Implications for joint therapy
Menarim, B. C., Gillis, K. H., Oliver, A., Mason, C., Werre, S. R., Luo, X., Byron, C. R., Kalbfleisch, T., MacLeod, J. N., & Dahlgren, L. A. (2020) · The FASEB Journal · doi:10.1096/fj.201902698r · Cited by 26
Hydroxytyrosol: A Promising Therapeutic Agent for Mitigating Inflammation and Apoptosis
Batarfi, W. A., Yunus, M. H. M., Hamid, A. A., Lee, Y. T., & Maarof, M. (2024) · Pharmaceutics · doi:10.3390/pharmaceutics16121504 · Cited by 25
Lipoxins and synthetic lipoxin mimetics: Therapeutic potential in renal diseases
Andrews, D. C., & Godson, C. (2021) · Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids · doi:10.1016/j.bbalip.2021.158940 · Cited by 27
Complement activation links inflammation to dental tissue regeneration
Bergmann, M., Jeanneau, C., Giraud, T., Richard, G., & About, I. (2020) · Clinical Oral Investigations · doi:10.1007/s00784-020-03621-w · Cited by 24
“This is followed by the inflammation resolution which is regulated by multiple mediators and immune cells [3].”
Background
Blood-based biomarkers of chronic inflammation
Pritzker, K. P. H. (2023) · Expert Review of Molecular Diagnostics · doi:10.1080/14737159.2023.2215928 · Cited by 24
Promising Antioxidant Activity of Erythrina Genus: An Alternative Treatment for Inflammatory Pain?
Cabrera, T. J., Bautista, M., Velázquez, C., Jaramillo‐Morales, O. A., Guerrero-Solano, J. A., Urrutia-Hernández, T. A., & la O‐Arciniega, M. D. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms22010248 · Cited by 27
“Several mediators are involved in the inflammatory pathway, prostaglandins, leukotrienes, cytokines, plateletactivating factor, and chemokines [89].”
Background
The role of miR-155 on liver diseases by modulating immunity, inflammation and tumorigenesis
Xue, X., Wang, J., Fu, K., Dai, S., Wu, R. T., Peng, C., & Li, Y. (2023) · International Immunopharmacology · doi:10.1016/j.intimp.2023.109775 · Cited by 24
Effects of fermented dairy products on inflammatory biomarkers: A meta-analysis
Zhang, X., Luo, Q., Guan, X.-X., Tang, Y., Chen, X., Deng, J., & Fan, J. (2022) · Nutrition Metabolism and Cardiovascular Diseases · doi:10.1016/j.numecd.2022.12.014 · Cited by 25
Epithelial Barrier: Protector and Trigger of Allergic Disorders
Izquierdo, E., Rodríguez‐Coira, J., Dolset, M. I. D., Gómez‐Casado, C., Barber, D., & Escribese, M. M. (2022) · Journal of Investigational Allergology and Clinical Immunology · doi:10.18176/jiaci.0779 · Cited by 24
“…tissue does not return to previous homeostasis, but rather achieves an adapted homeostatic state in which, despite recovery of organ architecture and function, there are changes in cellular composition and phenotype, thus affecting the severity of future inflammatory responses [143,158,159].”
Background
Pro-Resolving Mediator Resolvin E1 Restores Alveolar Fluid Clearance in Acute Respiratory Distress Syndrome
Luo, J., Zhang, W.-Y., Li, H., Zhang, P.-H., Tian, C., Wu, C.-H., Zhao, A.-N., Chen, M.-L., Guo, Y.-F., Cho, Y.-C., et al. (2021) · Shock · doi:10.1097/shk.0000000000001865 · Cited by 21
“Previous studies report that ChemR23 and BLT1 are specific receptors for RvE1 (20).”
Background
Inflammation and Exosomes in Fabry Disease Pathogenesis
Coelho-Ribeiro, B., Silva, H., Sampaio‐Marques, B., Fraga, A. G., Azevedo, O. M., Pedrosa, J., & Ludovico, P. (2024) · Cells · doi:10.3390/cells13080654 · Cited by 20
Effects of statins on specialized pro-resolving mediators: An additional pathway leading to resolution of inflammation
Radbakhsh, S., Katsiki, N., Santos, R. D., Mikhailidis, D. P., Mantzoros, C. S., & Sahebkar, A. (2022) · Metabolism · doi:10.1016/j.metabol.2022.155211 · Cited by 20
A multifunctional nanoparticle for efferocytosis and pro-resolving-mediated endometriosis therapy
Sun, Q., Lei, Y., Zhang, H., Ding, X., Yang, M., Zhang, T., Chen, J., Huang, Z., Wang, L., Lan, J., et al. (2022) · Colloids and Surfaces B Biointerfaces · doi:10.1016/j.colsurfb.2022.112893 · Cited by 22
Resolution pharmacology and the treatment of infectious diseases
Costa, V. V., Resende, F., Melo, E. M., & Teixeira, M. M. (2024) · British Journal of Pharmacology · doi:10.1111/bph.16323 · Cited by 19
“A review of the data that has led to their classification as pro-resolving molecules is beyond the scope of the current review but can be found in other recent reviews on the subject (see Feehan & Gilroy, 2019; Panigrahy et al., 2021; Sugimoto et al., 2019).”
Background
Amelioration of TPA-induced skin inflammation by the leaf extract of Vernonia amygdalina involves ERK/STAT3 (Ser727) signaling inhibition
Wu, J., Xie, J., Chen, Y., Fu, X., Wang, R., Deng, Y.-Y., Wang, S., Yu, H., Liang, C., & Yu, Z. (2022) · Phytomedicine · doi:10.1016/j.phymed.2022.154194 · Cited by 20
The Use of Specialized Pro-Resolving Mediators in Biomaterial-Based Immunomodulation
Sousa, A. B., & Barbosa, J. N. (2023) · Journal of Functional Biomaterials · doi:10.3390/jfb14040223 · Cited by 21
“(Cys-SPMs) and n-3 docosapentaenoic acid (DPA)-derived SPMs (n-3 DPA-derived SPMs) [18].”
BackgroundInfluential
METTL1-mediated m 7 G methylation of Sarm1 mRNA promotes macrophage inflammatory responses and multiple organ injury
Hou, C., Zhang, X., Wei, J., Wang, J.-N., Gao, J., Wang, Z.-J., Xie, S.-S., Chen, T., Sun, T., Pu, T., et al. (2025) · Science Immunology · doi:10.1126/sciimmunol.adv4810 · Cited by 22
NLRP3 Inflammasome: a Novel Insight into Heart Failure
Wang, Y., Li, Y., Zhang, W., Yuan, Z., Lv, S., & Zhang, J. (2022) · Journal of Cardiovascular Translational Research · doi:10.1007/s12265-022-10286-1 · Cited by 19
“Inflammation is the organism’s first immune defense against harmful stimuli, which occurs when the organism receives exogenous infection and endogenous cell tissue damage [11, 12].”
Background
UV radiation recruits CD4+GATA3+ and CD8+GATA3+ T cells while altering the lipid microenvironment following inflammatory resolution in human skin in vivo
Hawkshaw, N. J., Pilkington, S. M., Murphy, S. A., Al‐Gazaq, N., Farrar, M. D., Watson, R. E. B., Nicolaou, A., & Rhodes, L. E. (2020) · Clinical & Translational Immunology · doi:10.1002/cti2.1104 · Cited by 18
“initiating inflammatory signal has subsided, a beneficial state of local immunosuppression remains.(8) This post-resolution phase is characterised by either a secondary infiltrate(9,10) or retention of immune cells following inflammatory resolution, and maintains an immunosuppressive environment.”
Background
Panaxadiol inhibits IL-1β secretion by suppressing zinc finger protein 91-regulated activation of non-canonical caspase-8 inflammasome and MAPKs in macrophages.
Wang, J.-Y., Xing, Y.-X., Li, M.-Y., Zhang, Z.-H., Jin, H.-L., Ma, J., Lee, J., Zhong, Y., Zuo, H.-X., & Jin, X.-J. (2021) · Journal of Ethnopharmacology · doi:10.1016/j.jep.2021.114715 · Cited by 16
Signaling Pathways in Inflammation and Its Resolution: New Insights and Therapeutic Challenges
Cicala, C., & Morello, S. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms241311055 · Cited by 16
“In recent years, the research in this field has been working towards clarifying these pro-resolving pathways and signaling pathways that may be targets for therapeutic intervention [1,2].”
Background
Redox-sensitive high mobility group box 1 (HMGB1) is a multifunctional regulator of cellular senescence, inflammation, and immunosuppression: Impact on the aging process
Salminen, A. (2025) · Ageing Research Reviews · doi:10.1016/j.arr.2025.102926 · Cited by 15
Bone marrow mononuclear cells for joint therapy: The role of macrophages in inflammation resolution and tissue repair
Menarim, B. C., MacLeod, J. N., & Dahlgren, L. A. (2021) · World Journal of Stem Cells · doi:10.4252/wjsc.v13.i7.825 · Cited by 16
Mesenchymal stromal cells and alpha-1 antitrypsin have a strong synergy in modulating inflammation and its resolution
Han, L., Wu, X., Wang, O., Luan, X., Velander, W. H., Aynardi, M. C., Halstead, E. S., Bonavia, A. S., Jin, R., Li, G., et al. (2023) · Theranostics · doi:10.7150/thno.83942 · Cited by 14
“These mechanisms, designed to work together to prevent severe inflammation, often fail in patients with severe medical comorbidities and/or compromised immunity [3,4].”
3α-Angeloyloxy-ent-kaur-16-en-19-oic Acid Isolated from Wedelia trilobata L. Alleviates Xylene-Induced Mouse Ear Edema and Inhibits NF-κB and MAPK Pathway in LPS-Stimulated Macrophages
Xu, J., Zhou, L., Sun, L., Wang, Z., Wang, Y., Wang, Y., & He, X. (2020) · Journal of Natural Products · doi:10.1021/acs.jnatprod.0c00990 · Cited by 15
Diversity-oriented synthesis of diterpenoid alkaloids yields a potent anti-inflammatory agent
Li, X., Zhang, J., Chen, Q., Tang, P., Zhang, T., Feng, Q., Chen, J., Liu, Y., Peng, C. Y., Peng, C. Y., et al. (2023) · Phytomedicine · doi:10.1016/j.phymed.2023.154907 · Cited by 14
Tonic Meningeal Interleukin-10 Upregulates Delta Opioid Receptor to Prevent Relapse to Pain
Inyang, K. E., Sim, J., Clark, K. B., Geron, M., Monahan, K., Evans, C., O’Connell, P., Laumet, S., Peng, B., Ma, J., et al. (2023) · Brain Behavior and Immunity · doi:10.1016/j.bbi.2024.09.031 · Cited by 14
Flaxseed Ethanol Extract Effect in Acute Experimental Inflammation
Chera, E. I., Pop, T. I., Pop, R. M., Pârvu, M., Uifălean, A., Cătoi, A. F., Cecan, A. D., Mîrza, C.-M., Achimaș-Cădariu, P., & Pârvu, A. E. (2022) · Medicina · doi:10.3390/medicina58050582 · Cited by 15
“Moreover, it was suggested that this can be a risk for the development of chronic inflammation [1], because, in many chronic conditions, the”
Background
Absence of CCR2 Promotes Proliferation of Alveolar Macrophages That Control Lung Inflammation in Acute Respiratory Distress Syndrome in Mice
de Oliveira, V. L. S., Pollenus, E., Berghmans, N., Queiroz‐Junior, C. M., Blanter, M., Mattos, M. S., Teixeira, M. M., Proost, P., den Steen, P. E. V., Amaral, F. A., et al. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms232112920 · Cited by 14
“The resolution of lung inflammation requires an orchestrated immune response and several control mechanisms to avoid excessive inflammation and chronic disease [28,29].”
Background
Controlling Inflammation Improves Aging Skeletal Muscle Health
Fountain, W. A., Naruse, M., Claiborne, A., Trappe, S. W., & Trappe, T. A. (2023) · Exercise and Sport Sciences Reviews · doi:10.1249/jes.0000000000000313 · Cited by 15
Genome editing of PAR2 through targeted delivery of CRISPR-Cas9 system for alleviating acute lung inflammation via ERK/NLRP3/IL-1β and NO/iNOS signalling
Zhuo, X., Wu, Y., Fu, X., Li, J., Xiang, Y., Liang, X., Mao, C., & Jiang, Y. (2023) · Acta Pharmaceutica Sinica B · doi:10.1016/j.apsb.2023.08.013 · Cited by 12
A single dose of angiotensin-(1–7) resolves eosinophilic inflammation and protects the lungs from a secondary inflammatory challenge
Magalhães, G. S., Gregório, J. F., Beltrami, V. A., Félix, F. B., Oliveira-Campos, L., Bonilha, C. S., Righetti, R. F., Tibério, I. D. F. L. C., Sousa, F. B. D., Rezende, B. M., et al. (2024) · Inflammation Research · doi:10.1007/s00011-024-01880-x · Cited by 12

Authors: Feehan, K. T., & Gilroy, D. W.
Affiliations: University College London (GB)
Corresponding author: Gilroy, Derek W.
ORCID: Feehan, Karen T.
Gilroy, Derek W.
Venue: Trends in Molecular Medicine
Publisher: Elsevier BV
Published: 2019-03
Volume: 25
Issue: 3
Pages: 198-214
ISSN: 1471-4914 (ISSN-L)
DOI: 10.1016/j.molmed.2019.01.006
OpenAlex: W2918019780
Cited by: 229
References: 148
Citations by year: 2026: 22 · 2025: 32 · 2024: 40 · 2023: 43 · 2022: 37 · 2021: 30 · 2020: 22 · 2019: 3
FWCI: 3.11
Type: journal article
Language: en
Open access: green
discovery.ucl.ac.uk
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
www.elsevier.com/legal/tdmrep-license (tdm)
Locations: Trends in Molecular Medicine (publishedVersion)
PubMed (publishedVersion)
UCL Discovery (University College London) (submittedVersion)
Funders: Biotechnology and Biological Sciences Research Council (1788941)
Topics: Health Sciences › Nursing › Nutrition and Dietetics › Fatty Acid Research and Health
Life Sciences › Immunology and Microbiology › Immunology › Phagocytosis and Immune Regulation
Life Sciences › Immunology and Microbiology › Immunology › Immune Response and Inflammation
Keywords: inflammation resolution, chronic inflammation, autoimmune disease, innate immunity, adaptive homeostasis, tissue repair, inflammatory mediators
MeSH terms: Acute Disease, Animals, Chronic Disease, Disease Susceptibility, Humans, Immunity, Inflammation, Signal Transduction, Biomarkers, Cytokines, Inflammation Mediators

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Is Resolution the End of Inflammation?

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