Immunonutrition suppresses acute inflammatory responses through modulation of resolvin E1 in patients undergoing major hepatobiliary resection

Uno, Hiroyuki; Furukawa, Katsunori; Suzuki, Daisuke; Shimizu, Hiroaki; Ohtsuka, Masayuki; Kato, Atsushi; Yoshitomi, Hideyuki; Miyazaki, Masaru

doi:10.1016/j.surg.2016.01.019

Cited by 57 publications

(81 citation statements)

References 34 publications

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“…In the supplemented patients, systemic EPA levels increased and rapidly normalized when oral IMPACT uptake was stopped. EPA intake had no influence on plasma RvE1-levels which were about 1 µg/mL, and much higher when compared to other studies where levels are in the pg/mL-range [124,125]. Of note, levels of RvE1 were induced in both groups immediately after the surgery.…”

Section: Molecules Involved In Resolution Of Inflammationcontrasting

confidence: 54%

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Pro-Resolving Molecules—New Approaches to Treat Sepsis?

Buechler

Pohl

Aslanidis

2017

IJMS

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Inflammation is a complex response of the body to exogenous and endogenous insults. Chronic and systemic diseases are attributed to uncontrolled inflammation. Molecules involved in the initiation of inflammation are very well studied while pathways regulating its resolution are insufficiently investigated. Approaches to down-modulate mediators relevant for the onset and duration of inflammation are successful in some chronic diseases, while all of them have failed in sepsis patients. Inflammation and immune suppression characterize sepsis, indicating that anti-inflammatory strategies alone are inappropriate for its therapy. Heme oxygenase 1 is a sensitive marker for oxidative stress and is upregulated in inflammation. Carbon monoxide, which is produced by this enzyme, initiates multiple anti-inflammatory and pro-resolving activities with higher production of omega-3 fatty acid-derived lipid metabolites being one of its protective actions. Pro-resolving lipids named maresins, resolvins and protectins originate from the omega-3 fatty acids eicosapentaenoic acid and docosahexaenoic acid while lipoxins are derived from arachidonic acid. These endogenously produced lipids do not simply limit inflammation but actively contribute to its resolution, and thus provide an opportunity to combat chronic inflammatory diseases and eventually sepsis.

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Section: Molecules Involved In Resolution Of Inflammationcontrasting

confidence: 54%

“…Patients with omega-3 fatty acid intake had a more distinct RvE1 increase and a lesser postoperative raise of IL-6. Further, postoperative complications were less severe in patients with “immunonutrition” [125]. …”

Section: Molecules Involved In Resolution Of Inflammationmentioning

confidence: 99%

Pro-Resolving Molecules—New Approaches to Treat Sepsis?

Buechler

Pohl

Aslanidis

2017

IJMS

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“…Hence, our results suggest a potential physiologic mechanism by which coagulation initiates the endogenous production of functional n-3-derived SPMs that affect innate immune cells. Because the physiologic coagulation of blood is protective in humans, SPM production by clots may be of direct relevance to pathophysiology events in surgery (41), infection (11, 27, 42, 43), vascular inflammation (44, 45), stroke, and cancer (46, 47). …”

Section: Discussionmentioning

confidence: 99%

A cluster of immunoresolvents links coagulation to innate host defense in human blood

et al. 2017

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Blood coagulation is a protective response that prevents excessive bleeding upon blood vessel injury. Here, we investigated the relationship between coagulation and the resolution of inflammation and infection by lipid mediators (LMs) through metabololipidomic-based profiling of human whole blood (WB) during coagulation. We identified temporal clusters of endogenously produced pro-thrombotic and proinflammatory LMs (eicosanoids), as well as specialized proresolving mediators (SPMs). In addition to eicosanoids, a specific SPM cluster was identified that consisted of resolvin E1 (RvE1), RvD1, RvD5, lipoxin B4, and maresin 1, each of which was present at bioactive concentrations (0.1 to 1 nM). Removal of adenosine from the coagulating blood markedly enhanced the amounts of SPMs produced and further increased the biosynthesis of RvD3, RvD4, and RvD6. The cyclooxygenase inhibitors celecoxib and indomethacin, which block the production of thomboxanes and prostanoids, did not block the production of clot-driven SPMs. Unbiased mass cytometry analysis demonstrated that the SPM cluster produced in human blood targeted leukocytes at the single-cell level, directly activating ERK and CREB signaling in neutrophils and CD14+ monocytes. Treatment of human whole blood with the components of this SPM cluster enhanced both the phagocytosis and killing of Escherichia coli by leukocytes. Together, these data identify a pro-resolving LM circuit, including endogenous molecular brakes and accelerators, which promoted host defense. These temporal LM-SPM clusters can provide accessible metabolomic profiles for precision and personalized medicine.

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“…Additionally, in subgroup analysis there was a trend toward decreased mortality in patients who received n-3 fatty acids via enteral nutrition. In a cohort of subjects undergoing major hepatobiliary operations, it was found that preoperative treatment with EPA for 5 days lead to significantly increased plasma RvE1 levels and fewer infectious complications, as well as overall lesser severity of complications, compared to a control group (Uno, Furukawa et al 2016). Collectively, these studies begin to set the stage for future investigation of the effects of oral SPM or their precursors in the setting of an acute vascular intervention.…”

Section: Translation: Resolution Pharmacology In Vascular Injurymentioning

confidence: 96%

Resolution of vascular injury: Specialized lipid mediators and their evolving therapeutic implications

Mottola

Schaller

et al. 2017

Molecular Aspects of Medicine

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Acute vascular injury occurs in a number of important clinical contexts, including spontaneous disease-related events (e.g. plaque rupture, thrombosis) and therapeutic interventions such as angioplasty, stenting, or bypass surgery. Endothelial cell (EC) disruption exposes the underlying matrix, leading to a rapid deposition of platelets, coagulation proteins, and leukocytes. A thrombo-inflammatory response ensues characterized by leukocyte recruitment, vascular smooth muscle cell (VSMC) activation, and the elaboration of cytokines, reactive oxygen species and growth factors within the vessel wall. A resolution phase of vascular injury may be described in which leukocyte efflux, clearance of debris, and re-endothelialization occurs. VSMC migration and proliferation leads to the development of a thickened neointima that may lead to lumen compromise. Subsequent remodeling involves matrix protein deposition, and return of EC and VSMC to quiescence. Recent studies suggest that specialized proresolving lipid mediators (SPM) modulate key aspects of this response, and may constitute an endogenous homeostatic pathway in the vasculature. SPM exert direct effects on vascular cells that counteract inflammatory signals, reduce leukocyte adhesion, and inhibit VSMC migration and proliferation. These effects appear to be largely G-protein coupled receptor-dependent. Across a range of animal models of vascular injury, including balloon angioplasty, bypass grafting, and experimental aneurysm formation, SPM accelerate repair and reduce lesion formation. With bioactivity in the pM-nM range, a lack of discernible cytotoxicity, and a spectrum of vasculo-protective properties, SPM represent a novel class of vascular therapeutics. This review summarizes current research in this field, including a consideration of critical next steps and challenges in translation.

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Immunonutrition suppresses acute inflammatory responses through modulation of resolvin E1 in patients undergoing major hepatobiliary resection

Cited by 57 publications

References 34 publications

Pro-Resolving Molecules—New Approaches to Treat Sepsis?

Pro-Resolving Molecules—New Approaches to Treat Sepsis?

A cluster of immunoresolvents links coagulation to innate host defense in human blood

Resolution of vascular injury: Specialized lipid mediators and their evolving therapeutic implications

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