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Targeting Leukotrienes as a Therapeutic Strategy to Prevent Comorbidities Associated with Metabolic Stress

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Druggable Lipid Signaling Pathways

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 1274))

Abstract

Leukotrienes (LTs) are potent lipid mediators that exert a variety of functions, ranging from maintaining the tone of the homeostatic immune response to exerting potent proinflammatory effects. Therefore, LTs are essential elements in the development and maintenance of different chronic diseases, such as asthma, arthritis, and atherosclerosis. Due to the pleiotropic effects of LTs in the pathogenesis of inflammatory diseases, studies are needed to discover potent and specific LT synthesis inhibitors and LT receptor antagonists. Even though most clinical trials using LT inhibitors or antagonists have failed due to low efficacy and/or toxicity, new drug development strategies are driving the discovery for LT inhibitors to prevent inflammatory diseases. A newly important detrimental role for LTs in comorbidities associated with metabolic stress has emerged in the last few years and managing LT production and/or actions could represent an exciting new strategy to prevent or treat inflammatory diseases associated with metabolic disorders. This review is intended to shed light on the synthesis and actions of leukotrienes, the most common drugs used in clinical trials, and discuss the therapeutic potential of preventing LT function in obesity, diabetes, and hyperlipidemia.

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Authors and Affiliations

  1. Department of Immunology, University of Sao Paulo, Sao Paulo, Brazil

    Theresa Ramalho & Nayara Pereira

  2. Division of Infectious Diseases, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, USA

    Stephanie L. Brandt & C. Henrique Serezani

  3. Department of Pathology, Microbiology, and Immunology, Vanderbilt University Medical Center, Nashville, TN, USA

    C. Henrique Serezani

  4. Vanderbilt Institute for Inflammation, infection, and immunity (VI4), Vanderbilt University Medical Center, Nashville, TN, USA

    C. Henrique Serezani

  5. Vanderbilt Center for Immunobiology (VCI), Vanderbilt University Medical Center, Nashville, TN, USA

    C. Henrique Serezani

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  1. Theresa Ramalho
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  2. Nayara Pereira
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  3. Stephanie L. Brandt
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  4. C. Henrique Serezani
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Correspondence to C. Henrique Serezani .

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  1. Sanford Burnham Prebys Medical Discovery Institute, La Jolla, CA, USA

    Yasuyuki Kihara

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Ramalho, T., Pereira, N., Brandt, S.L., Serezani, C.H. (2020). Targeting Leukotrienes as a Therapeutic Strategy to Prevent Comorbidities Associated with Metabolic Stress. In: Kihara, Y. (eds) Druggable Lipid Signaling Pathways. Advances in Experimental Medicine and Biology, vol 1274. Springer, Cham. https://doi.org/10.1007/978-3-030-50621-6_4

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