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Sphingolipids: A Potential Molecular Approach to Treat Allergic Inflammation

DOI: 10.1155/2012/154174

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Abstract:

Allergic inflammation is an immune response to foreign antigens, which begins within minutes of exposure to the allergen followed by a late phase leading to chronic inflammation. Prolonged allergic inflammation manifests in diseases such as urticaria and rhino-conjunctivitis, as well as chronic asthma and life-threatening anaphylaxis. The prevalence of allergic diseases is profound with 25% of the worldwide population affected and a rising trend across all ages, gender, and racial groups. The identification and avoidance of allergens can manage this disease, but this is not always possible with triggers being common foods, prevalent air-borne particles and only extremely low levels of allergen exposure required for sensitization. Patients who are sensitive to multiple allergens require prophylactic and symptomatic treatments. Current treatments are often suboptimal and associated with adverse effects, such as the interruption of cognition, sleep cycles, and endocrine homeostasis, all of which affect quality of life and are a financial burden to society. Clearly, a better therapeutic approach for allergic diseases is required. Herein, we review the current knowledge of allergic inflammation and discuss the role of sphingolipids as potential targets to regulate inflammatory development in vivo and in humans. We also discuss the benefits and risks of using sphingolipid inhibitors. 1. Introduction Allergic inflammation can occur rapidly or delayed via the classical inflammatory immune reaction involving the production of specific IgE antibodies as well as the activation of inflammatory cells and the endothelium [1]. Many proinflammatory mediators and cytokines including histamine, leukotriene, and tumor necrosis factor α (TNFα) can activate the vascular endothelial cells (ECs) to cause pro-inflammatory microvasodilation and mediate leukocyte recruitment from the circulation to the sites of allergic inflammation [2, 3]. Excessive and prolonged leukocyte recruitment can result in extracellular matrix (ECM) remodelling and tissue damage [4]; thus controlling EC activation provides a strategy to minimize allergic inflammation. This review discusses the pathophysiology of vascular ECs during allergic inflammation, current treatments and new therapeutic approaches. We focus on the role of sphingolipids in the regulation of vasculature during the early phase of allergic inflammation, in particular, studies utilizing sphingolipid knockout animals which support their potential as new therapeutic targets. 2. Pathophysiology in Acute Allergic Inflammation Histamine is

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