Eicosanoid Mediators in the Airway Inflammation of Asthmatic Patients: What is New?

Abstract

Lipid mediators contribute to inflammation providing both pro-inflammatory signals and terminating the inflammatory process by activation of macrophages. Among the most significant biologically lipid mediators, these are produced by free-radical or enzymatic oxygenation of arachidonic acid named "eicosanoids". There were some novel eicosanoids identified within the last decade, and many of them are measurable in clinical samples by affordable chromatography-mass spectrometry equipment or sensitive immunoassays. In this review, we present some recent advances in understanding of the signaling by eicosanoid mediators during asthmatic airway inflammation. Eicosanoid profiling in the exhaled breath condensate, induced sputum, or their metabolites measurements in urine is complementary to the cellular phenotyping of asthmatic inflammation. Special attention is paid to aspirin-exacerbated respiratory disease, a phenotype of asthma manifested by the most profound changes in the profile of eicosanoids produced. A hallmark of this type of asthma with hypersensitivity to non-steroid anti-inflammatory drugs (NSAIDs) is to increase biosynthesis of cysteinyl leukotrienes on the systemic level. It depends on transcellular biosynthesis of leukotriene C4 by platelets that adhere to granulocytes releasing leukotriene A4. However, other abnormalities are also reported in this type of asthma as a resistance to anti-inflammatory activity of prostaglandin E2 or a robust eosinophil interferon-γ response resulting in cysteinyl leukotrienes production. A novel mechanism is also discussed in which an isoprostane structurally related to prostaglandin E2 is released into exhaled breath condensate during a provoked asthmatic attack. However, it is concluded that any single eicosanoid or even their complex profile can hardly provide a thorough explanation for the mechanism of asthmatic inflammation.

Eicosanoid mediator profiles in different phenotypes of nonsteroidal anti‐inflammatory drug‐induced urticaria

“…The inhibition of COX‐1 and the subsequent generation of inflammatory mediators from the arachidonic acid pathway have long been recognized as holding a central role in the etiopathogenesis of NERD and are also thought to participate in NECD . This mechanism has also been hypothesized to extend to NIUA, even in the absence of experimental data …”

“…According to the cyclooxygenase (COX)‐1 hypothesis, the inhibition of this enzyme by NSAIDs shunts the metabolism of arachidonic acid from the production of prostaglandins toward the 5‐lipoxygenase pathway, with the subsequent biosynthesis of cysteinyl (Cys)‐LTs (LTC4, LTD4, and LTE4) responsible for eliciting the clinical response in susceptible individuals . CysLTs play a role in eosinophil chemotaxis, vascular leakage, and airway remodeling, and are thought to be key proinflammatory mediators in cross‐hypersensitivity to NSAIDs . The COX‐1 hypothesis was first proposed to explain the etiology of NERD, supported by studies that found increased concentrations of LTE4 in urine, and nasal and bronchoalveolar lavage fluids after oral aspirin (ASA) challenge in patients with this pathology.…”

Metabolomic Insights Into the Synergistic Effect of Biapenem in Combination With Xuebijing Injection Against Sepsis

“…In addition, lipolysis, an adaptive response to inflammation (Fong et al, 1990), together with increased biosynthesis and decreased oxidation in liver, leading to the accumulation of FFAs in plasma of septic rats (Kamisoglu et al, 2013). The increased arachidonic acid, a precursor of proinflammation eicosanoid mediators (Sanak, 2016), might be closely related to the systemic inflammation reaction in sepsis. Sphingolipids are important building blocks of cell membranes, and a large of evidences have demonstrated that sphingolipid metabolites participate in many cell regulation processes as key signal molecules in immunity and inflammation (Michael and Sarah, 2014).…”

The Biology of Prostaglandins and Their Role as a Target for Allergic Airway Disease Therapy

“…Although aspirin-exacerbated respiratory disease (AERD) is not induced by the IgE-mediated hypersensitivity reaction, it is characterized by asthma, eosinophilic nasal polyposis, and nonsteroidal anti-inflammatory drug (NSAID) sensitivity, and it is a serious airway disease that affects both the upper and the lower airways [8]. AERD is dominantly regulated by lipid mediators such as PGs and leukotrienes (LTs) because the disease pathogenesis is characterized by alteration of AA metabolism [9,10]. In humans, COX-1 and COX-2 comprise the functional COX enzymes, whereas COX-3, which is encoded by COX-1, does not have known function yet.…”