Title: Inflammation resolution: a dual-pronged approach to averting cytokine storms in COVID-19?
Authors: Panigrahy, Dipak; Gilligan, Molly M; Huang, Sui; Gartung, Allison; Cortés-Puch, Irene; Sime, Patricia J; Phipps, Richard P; Serhan, Charles N; Hammock, Bruce D
Published In Cancer Metastasis Rev, (2020 06)
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.
PubMed ID:
32385712
MeSH Terms: Anti-Inflammatory Agents, Non-Steroidal/pharmacology; Anti-Inflammatory Agents, Non-Steroidal/therapeutic use*; Antiviral Agents/therapeutic use*; Betacoronavirus/immunology*; Betacoronavirus/isolation & purification; COVID-19; Clinical Trials as Topic; Coronavirus Infections/complications; Coronavirus Infections/drug therapy*; Coronavirus Infections/immunology; Coronavirus Infections/virology; Cytokine Release Syndrome/drug therapy*; Cytokine Release Syndrome/immunology; Cytokines/immunology; Cytokines/metabolism; Eicosanoids/immunology; Eicosanoids/metabolism; Epoxide Hydrolases/antagonists & inhibitors; Epoxide Hydrolases/metabolism; Humans; Macrophages/immunology; Macrophages/metabolism; Pandemics; Pneumonia, Viral/complications; Pneumonia, Viral/drug therapy*; Pneumonia, Viral/immunology; Pneumonia, Viral/virology; Pulmonary Alveoli/immunology; Pulmonary Alveoli/metabolism; Pulmonary Alveoli/virology; Respiratory Distress Syndrome/immunology; Respiratory Distress Syndrome/therapy*; SARS-CoV-2