Sphingolipids: A Potential Molecular Approach to Treat Allergic Inflammation

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.

Ceramide/sphingosine‐1‐phosphate imbalance is associated with distinct inflammatory phenotypes of uncontrolled asthma

“…Therefore, targeting the SL metabolic pathway could break a link of SL metabolism with airway inflammation. Pharmacological inhibition of SL metabolism has exhibited a promise as a novel therapeutic target for controlling chronic airway inflammation in patients with asthma . FTY‐720, a structural analog of sphingosine, and myriocin, an SPT inhibitor, could attenuate airway hyper‐responsiveness and inflammation by antagonizing S1P signaling and inhibiting ceramide synthesis .…”

“…Pharmacological inhibition of SL metabolism has exhibited a promise as a novel therapeutic target for controlling chronic airway inflammation in patients with asthma. 53 FTY-720, a structural analog of sphingosine, and myriocin, an SPT inhibitor, could attenuate airway hyper-responsiveness and inflammation by antagonizing S1P signaling 54,55 and inhibiting ceramide synthesis. 41,56 Considering their pleiotropic actions on various types of immune cells, careful examination on which inflammatory phenotype could be efficiently controlled by these pharmacological candidates should be beneficial.…”

Serum Sphingolipids Reflect the Severity of Chronic HBV Infection and Predict the Mortality of HBV-Acute-on-Chronic Liver Failure

“…Thus, the use of cell death-related sphingolipids to indicate HBV-ACLF status might represent a novel prognostic marker that can be used to better identify patients that require a liver transplant. On the other hand, sphingolipids are extensively involved in the function of the immune system [34] . Increasing evidence suggests that non-HBV-specific inflammation of the liver is likely responsible for the hepatic pathology observed in patients with CHB [35] .…”

The Role of Sphingolipids in Allergic Disorders

“…Sphingolipids and their intermediates are an extraordinarily diverse group of molecules with a vast array of physical properties, which are present in almost all eukaryotic organisms (9). Their basic structure is composed of a sphingoid base backbone attached by an amide bond to different fatty acids or a head group at the primary hydroxyl (3). The nature of the head group is highly variable, and it defines the different sphingolipid species: CER, in which the head group is substituted by hydrogen; sphingomyelins, in which the head group is substituted by phosphocholine; and cerebrosides or gangliosides, in which hundreds of different monosaccharides in a single or combined form make the compound (10,11).…”

“…Current treatments are often suboptimal, resulting in a reduced quality of life for the patients and placing an economic burden on society. A deeper understanding of their pathogenic mechanisms might lead to much needed and improved disease biomarkers ( 3 ).…”