Eicosanoid Storm in Infection and Inflammation

Overview

Journal Nat Rev Immunol

Specialty Allergy & Immunology

Date 2015 Jul 4

PMID 26139350

Citations 635

Authors

Edward A Dennis

Paul C Norris

Affiliations

Soon will be listed here.

Abstract

Controlled immune responses to infection and injury involve complex molecular signalling networks with coordinated and often opposing actions. Eicosanoids and related bioactive lipid mediators derived from polyunsaturated fatty acids constitute a major bioactive lipid network that is among the most complex and challenging pathways to map in a physiological context. Eicosanoid signalling, similar to cytokine signalling and inflammasome formation, has primarily been viewed as a pro-inflammatory component of the innate immune response; however, recent advances in lipidomics have helped to elucidate unique eicosanoids and related docosanoids with anti-inflammatory and pro-resolution functions. This has advanced our overall understanding of the inflammatory response and its therapeutic implications. The induction of a pro-inflammatory and anti-inflammatory eicosanoid storm through the activation of inflammatory receptors by infectious agents is reviewed here.

Citing Articles

Identification and verification of biomarkers associated with arachidonic acid metabolism in non-alcoholic fatty liver disease.

Li J, Su W, Wang Z, Ji X, Wang J, Wang K Sci Rep. 2025; 15(1):8521.

PMID: 40074804 PMC: 11903885. DOI: 10.1038/s41598-025-92972-z.

Bioactive lipid signaling and lipidomics in macrophage polarization: Impact on inflammation and immune regulation.

Rodriguez J, Casas J, Balboa M, Balsinde J Front Immunol. 2025; 16:1550500.

PMID: 40028333 PMC: 11867965. DOI: 10.3389/fimmu.2025.1550500.

Lipidomic insights on abdominal aortic aneurysm and peripheral arterial disease.

Ferreira H, Trindade F, Nogueira-Ferreira R, Leite-Moreira A, Ferreira R, Dias-Neto M J Mol Med (Berl). 2025; .

PMID: 40011252 DOI: 10.1007/s00109-025-02524-1.

Systematic review of innate immune responses against complex infection in animal models.

Nieto Ramirez L, Mehaffy C, Dobos K Front Immunol. 2025; 15:1467016.

PMID: 39949719 PMC: 11821578. DOI: 10.3389/fimmu.2024.1467016.

Gangliosides and Cholesterol: Dual Regulators of Neuronal Membrane Framework in Autism Spectrum Disorder.

Puljko B, Stracak M, Kalanj-Bognar S, Todoric Laidlaw I, Mlinac-Jerkovic K Int J Mol Sci. 2025; 26(3).

PMID: 39941090 PMC: 11818915. DOI: 10.3390/ijms26031322.

References

Tam V, Quehenberger O, Oshansky C, Suen R, Armando A, Treuting P . Lipidomic profiling of influenza infection identifies mediators that induce and resolve inflammation. Cell. 2013; 154(1):213-27. PMC: 3753192. DOI: 10.1016/j.cell.2013.05.052. View

Serhan C . Pro-resolving lipid mediators are leads for resolution physiology. Nature. 2014; 510(7503):92-101. PMC: 4263681. DOI: 10.1038/nature13479. View

Chen C . COX-2's new role in inflammation. Nat Chem Biol. 2010; 6(6):401-2. DOI: 10.1038/nchembio.375. View

Treffkorn L, Scheibe R, Maruyama T, Dieter P . PGE2 exerts its effect on the LPS-induced release of TNF-alpha, ET-1, IL-1alpha, IL-6 and IL-10 via the EP2 and EP4 receptor in rat liver macrophages. Prostaglandins Other Lipid Mediat. 2004; 74(1-4):113-23. DOI: 10.1016/j.prostaglandins.2004.07.005. View

Spik I, Brenuchon C, Angeli V, Staumont D, Fleury S, Capron M . Activation of the prostaglandin D2 receptor DP2/CRTH2 increases allergic inflammation in mouse. J Immunol. 2005; 174(6):3703-8. DOI: 10.4049/jimmunol.174.6.3703. View

Nebert D, Dalton T . The role of cytochrome P450 enzymes in endogenous signalling pathways and environmental carcinogenesis. Nat Rev Cancer. 2006; 6(12):947-60. DOI: 10.1038/nrc2015. View

Gross O, Thomas C, Guarda G, Tschopp J . The inflammasome: an integrated view. Immunol Rev. 2011; 243(1):136-51. DOI: 10.1111/j.1600-065X.2011.01046.x. View

Bray M, Cunningham F, Ford-Hutchinson A, Smith M . Leukotriene B4: a mediator of vascular permeability. Br J Pharmacol. 1981; 72(3):483-6. PMC: 2071580. DOI: 10.1111/j.1476-5381.1981.tb11000.x. View

Harmon G, Dumlao D, Ng D, Barrett K, Dennis E, Dong H . Pharmacological correction of a defect in PPAR-gamma signaling ameliorates disease severity in Cftr-deficient mice. Nat Med. 2010; 16(3):313-8. PMC: 2834836. DOI: 10.1038/nm.2101. View

10.

Basu S . Novel cyclooxygenase-catalyzed bioactive prostaglandin F2alpha from physiology to new principles in inflammation. Med Res Rev. 2006; 27(4):435-68. DOI: 10.1002/med.20098. View

11.

Balsinde J, Balboa M, Dennis E . Antisense inhibition of group VI Ca2+-independent phospholipase A2 blocks phospholipid fatty acid remodeling in murine P388D1 macrophages. J Biol Chem. 1997; 272(46):29317-21. DOI: 10.1074/jbc.272.46.29317. View

12.

Cheng K, Wu T, Wu K, Sturino C, Metters K, Gottesdiener K . Antagonism of the prostaglandin D2 receptor 1 suppresses nicotinic acid-induced vasodilation in mice and humans. Proc Natl Acad Sci U S A. 2006; 103(17):6682-7. PMC: 1458941. DOI: 10.1073/pnas.0601574103. View

13.

Jakobsson P, Thoren S, Morgenstern R, Samuelsson B . Identification of human prostaglandin E synthase: a microsomal, glutathione-dependent, inducible enzyme, constituting a potential novel drug target. Proc Natl Acad Sci U S A. 1999; 96(13):7220-5. PMC: 22058. DOI: 10.1073/pnas.96.13.7220. View

14.

Vane J . Biomedicine. Back to an aspirin a day?. Science. 2002; 296(5567):474-5. DOI: 10.1126/science.1071702. View

15.

Passarelli M, Ewing A, Winograd N . Single-cell lipidomics: characterizing and imaging lipids on the surface of individual Aplysia californica neurons with cluster secondary ion mass spectrometry. Anal Chem. 2013; 85(4):2231-8. PMC: 3867296. DOI: 10.1021/ac303038j. View

16.

Trostchansky A, Bonilla L, Thomas C, ODonnell V, Marnett L, Radi R . Nitroarachidonic acid, a novel peroxidase inhibitor of prostaglandin endoperoxide H synthases 1 and 2. J Biol Chem. 2011; 286(15):12891-900. PMC: 3075636. DOI: 10.1074/jbc.M110.154518. View

17.

Murakami K, Ide T, Suzuki M, Mochizuki T, Kadowaki T . Evidence for direct binding of fatty acids and eicosanoids to human peroxisome proliferators-activated receptor alpha. Biochem Biophys Res Commun. 1999; 260(3):609-13. DOI: 10.1006/bbrc.1999.0951. View

18.

Naraba H, Murakami M, Matsumoto H, Shimbara S, Ueno A, Kudo I . Segregated coupling of phospholipases A2, cyclooxygenases, and terminal prostanoid synthases in different phases of prostanoid biosynthesis in rat peritoneal macrophages. J Immunol. 1998; 160(6):2974-82. View

19.

Hurley B, Siccardi D, Mrsny R, McCormick B . Polymorphonuclear cell transmigration induced by Pseudomonas aeruginosa requires the eicosanoid hepoxilin A3. J Immunol. 2004; 173(9):5712-20. DOI: 10.4049/jimmunol.173.9.5712. View

20.

Patrono C, Baigent C . Nonsteroidal anti-inflammatory drugs and the heart. Circulation. 2014; 129(8):907-16. DOI: 10.1161/CIRCULATIONAHA.113.004480. View