Food and Behaviour Research

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Inflammation resolution: a dual-pronged approach to averting cytokine storms in COVID-19?

Panigrahy D, Gilligan MM, Huang S, Gartung A, Cortés-Puch I, Sime PJ, Phipps RP, Serhan CN, Hammock BD. (2020) Cancer Metastasis Rev.   May 8. doi: 10.1007/s10555-020-09889-4. [Epub ahead of print] 

Web URL: Read this and related abstracts via PubMed here. Free full text of this article is available online

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.

KEYWORDS:

COVID-19; Cytokine storms; Eicosanoid storm; Inflammation resolution; SARS-CoV-2

FAB RESEARCH COMMENT:

The immune-modulating substances discussed here (including 'eicosanoids' and 'resolvins') are made naturally within the body from EPA and DHA and are just some of the huge number of different regulatory substances - known as lipid mediators - derived from long-chain omega-3 and omega-6 fats. 

See the associated news article and FAB comments here:


And for more information on nutrition and immunity, see also: