The function of specialized pro-resolving endogenous lipid mediators, vitamins, and other micronutrients in the control of the inflammatory processes: Possible role in patients with SARS-CoV-2 related infection

Abstract

Inflammation is an essential protective response against harmful stimuli, such as invading pathogens, damaged cells, or irritants. Physiological inflammation eliminates pathogens and promotes tissue repair and healing. Effective immune response in humans depends on a tightly regulated balance among inflammatory and anti-inflammatory mechanisms involving both innate and adaptive arms of the immune system. Excessive inflammation can become pathological and induce detrimental effects. If this process is not self-limited, an inappropriate remodeling of the tissues and organs can occur and lead to the onset of chronic degenerative diseases. A wide spectrum of infectious and non-infectious agents may activate the inflammation, via the release of mediators and cytokines by distinct subtypes of lymphocytes and macrophages. Several molecular mechanisms regulate the onset, progression, and resolution of inflammation. All these steps, even the termination of this process, are active and not passive events. In particular, a complex interplay exists between mediators (belonging to the group of Eicosanoids), which induce the beginning of inflammation, such as Prostaglandins (PGE2), Leukotrienes (LT), and thromboxane A2 (TXA2), and molecules which display a key role in counteracting this process and in promoting its proper resolution. The latter group of mediators includes: ω-6 arachidonic acid (AA)-derived metabolites, such as Lipoxins (LXs), ω -3 eicosapentaenoic acid (EPA)-derived mediators, such as E-series Resolvins (RvEs), and ω -3 docosahexaenoic (DHA)-derived mediators, such as D-series Resolvins (RvDs), Protectins (PDs) and Maresins (MaRs). Overall, these mediators are defined as specialized pro-resolving mediators (SPMs). Reduced synthesis of these molecules may lead to uncontrolled inflammation with possible harmful effects. ω-3 fatty acids are widely used in clinical practice as rather inexpensive, safe, readily available supplemental therapy. Taking advantage of this evidence, several researchers are suggesting that SPMs may have beneficial effects in the complementary treatment of patients with severe forms of SARS-CoV-2 related infection, to counteract the “cytokine storm” observed in these individuals. Well-designed and sized trials in patients suffering from COVID-19 with different degrees of severity are needed to investigate the real impact in the clinical practice of this promising therapeutic approach.

Plasma Oxylipins and Their Precursors Are Strongly Associated with COVID-19 Severity and with Immune Response Markers

“…In animal models of inflammation, during the acute response phase a decrease was recorded in prostaglandin synthases [ 23 ] and a variety of AA eicosanoids [ 57 ], followed by an increase during the resolution phase. Therefore, we could expect that in our study, lower levels of prostanoids may hinder a shift from production of pro-inflammatory M1 macrophages towards the anti-inflammatory M2 macrophages, facilitated by prostanoids [ 6 ]. In addition, lower HETEs levels could hamper their conversion into the pro-resolving lipoxins [ 30 , 42 ].…”

“…Figure 5 concisely illustrates the metabolism of omega-3 fatty acids into SPMs and their intermediates, all expected to be rapidly recruited to inflammation cites to promote resolution and prevent tissue damage [ 6 , 30 , 64 ]. This recruitment, alongside high oxidative stress, may explain the elevated aLA, EPA, and peroxidation derivatives in the plasma of ICU patients.…”

“…A persistent and excessive innate immune response contributes to COVID-19 severity. Various lipids, some acting as immune modulators, are dysregulated along the course of the disease [ 1 , 2 , 3 , 4 , 5 , 6 ], yet obtaining an exact metabolic picture of small lipids involvement is still work in progress [ 5 , 7 , 8 , 9 , 10 ]. Low molecular weight lipids (<500 Da) play diverse biochemical roles, as they are embedded in cell membranes and take part in cell signalling, energy production and storage, among other endogenous processes.…”

“…In comparison, a consistent anti-inflammatory activity is attributed to AA-derived lipoxins, and to protectins, resolvins, and maresins produced from the omega-3 PUFAs eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). These specialised pro-resolving mediators (SPM) suppress microbial proliferation, inhibit inflammation, reduce organ fibrosis, and promote wound healing [ 6 , 9 , 28 , 29 , 30 ].…”

Awareness of the relationship between chemopreventive behaviours and occurrence of cancer in patients with selected types of cancer.

“…Substancje o udowodnionym działaniu chemoprewencyjnym oraz immunostymulującym to m.in. : związki fitochemiczne (polifenole, karotenoidy), składniki mineralne (wapń, selen, cynk, żelazo, miedź), błonnik pokarmowy, witaminy (A, D, E, C, B 6 , B 12 , B 9 ) wielonienasycone kwasy tłuszczowe z rodziny omega-3 oraz probiotyki i prebiotyki [5][6][7][8][15][16][17][18][19][20][21][22][23][24][25][26][27].…”