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Inflammation resolution: a dual-pronged approach to averting cytokine storms in COVID-19?
Cancer Metastasis Rev. 2020 06; 39(2):337-340.CM

Abstract

Severe coronavirus disease (COVID-19) is characterized by pulmonary hyper-inflammation and potentially life-threatening "cytokine storms". Controlling the local and systemic inflammatory response in COVID-19 may be as important as anti-viral therapies. Endogenous lipid autacoid mediators, referred to as eicosanoids, play a critical role in the induction of inflammation and pro-inflammatory cytokine production. SARS-CoV-2 may trigger a cell death ("debris")-induced "eicosanoid storm", including prostaglandins and leukotrienes, which in turn initiates a robust inflammatory response. A paradigm shift is emerging in our understanding of the resolution of inflammation as an active biochemical process with the discovery of novel endogenous specialized pro-resolving lipid autacoid mediators (SPMs), such as resolvins. Resolvins and other SPMs stimulate macrophage-mediated clearance of debris and counter pro-inflammatory cytokine production, a process called inflammation resolution. SPMs and their lipid precursors exhibit anti-viral activity at nanogram doses in the setting of influenza without being immunosuppressive. SPMs also promote anti-viral B cell antibodies and lymphocyte activity, highlighting their potential use in the treatment of COVID-19. Soluble epoxide hydrolase (sEH) inhibitors stabilize arachidonic acid-derived epoxyeicosatrienoic acids (EETs), which also stimulate inflammation resolution by promoting the production of pro-resolution mediators, activating anti-inflammatory processes, and preventing the cytokine storm. Both resolvins and EETs also attenuate pathological thrombosis and promote clot removal, which is emerging as a key pathology of COVID-19 infection. Thus, both SPMs and sEH inhibitors may promote the resolution of inflammation in COVID-19, thereby reducing acute respiratory distress syndrome (ARDS) and other life-threatening complications associated with robust viral-induced inflammation. While most COVID-19 clinical trials focus on "anti-viral" and "anti-inflammatory" strategies, stimulating inflammation resolution is a novel host-centric therapeutic avenue. Importantly, SPMs and sEH inhibitors are currently in clinical trials for other inflammatory diseases and could be rapidly translated for the management of COVID-19 via debris clearance and inflammatory cytokine suppression. Here, we discuss using pro-resolution mediators as a potential complement to current anti-viral strategies for COVID-19.

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Authors+Show Affiliations

Panigrahy D
Center for Vascular Biology Research, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, 02215, USA. dpanigra@bidmc.harvard.edu. Department of Pathology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, 02215, USA. dpanigra@bidmc.harvard.edu.
Gilligan MM
Center for Vascular Biology Research, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, 02215, USA. Department of Pathology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, 02215, USA.
Huang S
Institute for Systems Biology, Seattle, WA, 98109, USA.
Gartung A
Center for Vascular Biology Research, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, 02215, USA. Department of Pathology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, 02215, USA.
Cortés-Puch I
Division of Pulmonary, Critical Care and Sleep Medicine, University of California Davis Medical Center, Sacramento, CA, 95817, USA. EicOsis Human Health, Davis, CA, 95616, USA.
Sime PJ
Division of Pulmonary and Critical Care Medicine, Virginia Commonwealth University, Richmond, VA, 23298, USA.
Phipps RP
Independent scholar, Richmond, VA, 23233, USA.
Serhan CN
Center for Experimental Therapeutics and Reperfusion Injury, Department of Anesthesiology, Perioperative and Pain Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, 02115, USA. cserhan@bwh.harvard.edu.
Hammock BD
Department of Entomology and Nematology, and UCD Comprehensive Cancer Center, University of California, Davis, Davis, CA, 95616, USA. bdhammock@ucdavis.edu.

MeSH

Anti-Inflammatory Agents, Non-SteroidalAntiviral AgentsBetacoronavirusCOVID-19Clinical Trials as TopicCoronavirus InfectionsCytokine Release SyndromeCytokinesEicosanoidsEpoxide HydrolasesHumansMacrophagesPandemicsPneumonia, ViralPulmonary AlveoliRespiratory Distress SyndromeSARS-CoV-2

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

32385712

Clinical Trial Links

Glycine Supplement for Severe COVID-19
Vitamin D, Omega-3, and Combination Vitamins B, C and Zinc Supplementation for the Treatment and Prevention of COVID-19

Citation

Panigrahy, Dipak, et al. "Inflammation Resolution: a Dual-pronged Approach to Averting Cytokine Storms in COVID-19?" Cancer Metastasis Reviews, vol. 39, no. 2, 2020, pp. 337-340.
Panigrahy D, Gilligan MM, Huang S, et al. Inflammation resolution: a dual-pronged approach to averting cytokine storms in COVID-19? Cancer Metastasis Rev. 2020;39(2):337-340.
Panigrahy, D., Gilligan, M. M., Huang, S., Gartung, A., Cortés-Puch, I., Sime, P. J., Phipps, R. P., Serhan, C. N., & Hammock, B. D. (2020). Inflammation resolution: a dual-pronged approach to averting cytokine storms in COVID-19? Cancer Metastasis Reviews, 39(2), 337-340. https://doi.org/10.1007/s10555-020-09889-4
Panigrahy D, et al. Inflammation Resolution: a Dual-pronged Approach to Averting Cytokine Storms in COVID-19. Cancer Metastasis Rev. 2020;39(2):337-340. PubMed PMID: 32385712.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Inflammation resolution: a dual-pronged approach to averting cytokine storms in COVID-19? AU - Panigrahy,Dipak, AU - Gilligan,Molly M, AU - Huang,Sui, AU - Gartung,Allison, AU - Cortés-Puch,Irene, AU - Sime,Patricia J, AU - Phipps,Richard P, AU - Serhan,Charles N, AU - Hammock,Bruce D, PY - 2020/5/10/pubmed PY - 2020/7/7/medline PY - 2020/5/10/entrez KW - COVID-19 KW - Cytokine storms KW - Eicosanoid storm KW - Inflammation resolution KW - SARS-CoV-2 SP - 337 EP - 340 JF - Cancer metastasis reviews JO - Cancer Metastasis Rev VL - 39 IS - 2 N2 - Severe coronavirus disease (COVID-19) is characterized by pulmonary hyper-inflammation and potentially life-threatening "cytokine storms". Controlling the local and systemic inflammatory response in COVID-19 may be as important as anti-viral therapies. Endogenous lipid autacoid mediators, referred to as eicosanoids, play a critical role in the induction of inflammation and pro-inflammatory cytokine production. SARS-CoV-2 may trigger a cell death ("debris")-induced "eicosanoid storm", including prostaglandins and leukotrienes, which in turn initiates a robust inflammatory response. A paradigm shift is emerging in our understanding of the resolution of inflammation as an active biochemical process with the discovery of novel endogenous specialized pro-resolving lipid autacoid mediators (SPMs), such as resolvins. Resolvins and other SPMs stimulate macrophage-mediated clearance of debris and counter pro-inflammatory cytokine production, a process called inflammation resolution. SPMs and their lipid precursors exhibit anti-viral activity at nanogram doses in the setting of influenza without being immunosuppressive. SPMs also promote anti-viral B cell antibodies and lymphocyte activity, highlighting their potential use in the treatment of COVID-19. Soluble epoxide hydrolase (sEH) inhibitors stabilize arachidonic acid-derived epoxyeicosatrienoic acids (EETs), which also stimulate inflammation resolution by promoting the production of pro-resolution mediators, activating anti-inflammatory processes, and preventing the cytokine storm. Both resolvins and EETs also attenuate pathological thrombosis and promote clot removal, which is emerging as a key pathology of COVID-19 infection. Thus, both SPMs and sEH inhibitors may promote the resolution of inflammation in COVID-19, thereby reducing acute respiratory distress syndrome (ARDS) and other life-threatening complications associated with robust viral-induced inflammation. While most COVID-19 clinical trials focus on "anti-viral" and "anti-inflammatory" strategies, stimulating inflammation resolution is a novel host-centric therapeutic avenue. Importantly, SPMs and sEH inhibitors are currently in clinical trials for other inflammatory diseases and could be rapidly translated for the management of COVID-19 via debris clearance and inflammatory cytokine suppression. Here, we discuss using pro-resolution mediators as a potential complement to current anti-viral strategies for COVID-19. SN - 1573-7233 UR - https://www.unboundmedicine.com/medline/citation/32385712/Inflammation_resolution:_a_dual_pronged_approach_to_averting_cytokine_storms_in_COVID_19 DB - PRIME DP - Unbound Medicine ER -