Immune treatments for alcohol use disorder: A translational framework |
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| Affiliation: | 1. Department of Psychology, University of California, Los Angeles, Los Angeles, CA, USA;2. Department of Psychiatry and Biobehavioral Sciences, University of California, Los Angeles, Los Angeles, CA, USA;3. Jane and Terry Semel Institute for Neuroscience and Human Behavior, University of California at Los Angeles, Los Angeles, CA, USA;4. Cousins Center for Psychoneuroimmunology, University of California, Los Angeles, Los Angeles, CA, USA;1. Department of Psychology, Williams Hall, Ithaca College, 953 Danby Road, Ithaca, NY 14850, United States;2. Developmental Exposure Alcohol Research Center (DEARC), Behavioral Neuroscience Program, Department of Psychology, Binghamton University, Binghamton, NY 13902-6000, United States;1. Department of Psychiatry and Behavioral Sciences, Medical University of South Carolina, 67 President Street, MSC 861, Charleston, SC, United States;2. Department of Public Health Sciences, Medical University of South Carolina, 135 Cannon Street, Suite 303, MSC 835, Charleston, SC, United States;1. Bowles Center for Alcohol Studies, School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA;2. Department of Psychiatry, School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC 27514, USA;1. School of Pharmacy, Pharmacology Unit, University of Camerino, Camerino (MC) 62032, Italy;2. Department of Neurobiology and Developmental Sciences, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA;3. Omeros Corporation, Seattle, WA 98101, USA;4. Committee on the Neurobiology of Addictive Disorders, The Scripps Research Institute, La Jolla, CA 92037, USA |
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| Abstract: | While the immune system is essential for survival, an excessive or prolonged inflammatory response, such as that resulting from sustained heavy alcohol use, can damage the host and contribute to psychiatric disorders. A growing body of literature indicates that the immune system plays a critical role in the development and maintenance of alcohol use disorder (AUD). As such, there is enthusiasm for treatments that can restore healthy levels of inflammation as a mechanism to reduce drinking and promote recovery. In this qualitative literature review, we provide a conceptual rationale for immune therapies and discuss progress in medications development for AUD focused on the immune system as a treatment target. This review is organized into sections based on primary signaling pathways targeted by the candidate therapies, namely: (a) toll-like receptors, (b) phosphodiesterase inhibitors, (c) peroxisome proliferator-activated receptors, (d) microglia and astrocytes, (e) other immune pharmacotherapies, and (f) behavioral therapies. As relevant within each section, we examine the basic biological mechanisms of each class of therapy and evaluate preclinical research testing the role of the therapy on mitigating alcohol-related behaviors in animal models. To the extent available, translational findings are reviewed with discussion of completed and ongoing randomized clinical trials and their findings to date. An applied and clinically focused approach is taken to identify the potential clinical applications of the various treatments reviewed. We conclude by delineating the most promising candidate treatments and discussing future directions by considering opportunities for immune treatment development and personalized medicine for AUD. |
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| Keywords: | Alcohol use disorder Inflammation Medications development Immune system Neuroinflammation Heavy alcohol use Immune therapy Neuroimmune modulator Addiction |
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