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Biomolecules
Volume 16
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10.3390/biom16030427
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Article

High-Dose Ethanol-Induced Immunosuppression Modulates Sex-Specific Disease Outcomes in a Murine Model of Multiple Sclerosis

by
Adriana S. P. Nuncio
1,2,†,
Katherine Motovilov
1,3,†,
Max Weed
1,3,
Simali Shah
1,
Sam Bazzi
1,3,4,
Esha Idnani
1,
Turner Lime
5,
Daniela Carrizales Sauceda
5,
Regina A. Mangieri
5,
Cole Maguire
1,3,* and
Esther Melamed
1,3,6,*
1
Department of Neurology, Dell Medical School, The University of Texas at Austin, Austin, TX 78712, USA
2
Department of Molecular Biosciences, The University of Texas at Austin, Austin, TX 78712, USA
3
Department of Neuroscience, The University of Texas at Austin, Austin, TX 78712, USA
4
University of Texas Southwestern (UTSW) Medical School, UTSW Medical Center, Dallas, TX 75390, USA
5
Division of Pharmacology and Toxicology, College of Pharmacy, The University of Texas at Austin, Austin, TX 78712, USA
6
Department of Internal Medicine, Dell Medical School, The University of Texas at Austin, Austin, TX 78712, USA
*
Authors to whom correspondence should be addressed.
†
These authors contributed equally to this work.
Biomolecules 2026, 16(3), 427; https://doi.org/10.3390/biom16030427
Submission received: 3 February 2026 / Revised: 3 March 2026 / Accepted: 3 March 2026 / Published: 13 March 2026
(This article belongs to the Special Issue Alcohol-Related Organ Damage: Mechanisms, Outcomes, and Treatment Modalities)
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Abstract

Both epidemiological studies and prior work in animal models suggest that moderate-dose alcohol reduces disease severity across several autoimmune conditions, including multiple sclerosis (MS). However, the mechanisms underlying the potentially beneficial effects of alcohol and how these effects may change with alcohol dose in autoimmunity remain underexplored. In this study, we characterize the effects of chronic, high-dose ethanol consumption in experimental autoimmune encephalomyelitis (EAE), a murine model of MS, by examining EAE disease severity, gut microbial composition, and peripheral cell immunophenotypes. We found that high-dose ethanol-fed males exhibited a significant amelioration in peak EAE disease severity, in association with decreased T cell activation and B cell proportions. Concurrently, we observed proinflammatory shifts in gut microbiota and hepatic lipid accumulation. Our results suggest that high dose ethanol may benefit autoimmune neuroinflammation in EAE through immunosuppressive effects on adaptive immunity, however its toxic systemic effects preclude the use of alcohol as an immunomodulator in MS. Overall, our findings reveal a mechanistic basis for alcohol’s beneficial properties in autoimmunity and could inform the development of more targeted disease modifying therapies that recapitulate these benefits without alcohol-associated toxicity.
Keywords: alcohol; multiple sclerosis; EAE; gut microbiome; immune system; sex differences alcohol; multiple sclerosis; EAE; gut microbiome; immune system; sex differences

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MDPI and ACS Style

Nuncio, A.S.P.; Motovilov, K.; Weed, M.; Shah, S.; Bazzi, S.; Idnani, E.; Lime, T.; Sauceda, D.C.; Mangieri, R.A.; Maguire, C.; et al. High-Dose Ethanol-Induced Immunosuppression Modulates Sex-Specific Disease Outcomes in a Murine Model of Multiple Sclerosis. Biomolecules 2026, 16, 427. https://doi.org/10.3390/biom16030427

AMA Style

Nuncio ASP, Motovilov K, Weed M, Shah S, Bazzi S, Idnani E, Lime T, Sauceda DC, Mangieri RA, Maguire C, et al. High-Dose Ethanol-Induced Immunosuppression Modulates Sex-Specific Disease Outcomes in a Murine Model of Multiple Sclerosis. Biomolecules. 2026; 16(3):427. https://doi.org/10.3390/biom16030427

Chicago/Turabian Style

Nuncio, Adriana S. P., Katherine Motovilov, Max Weed, Simali Shah, Sam Bazzi, Esha Idnani, Turner Lime, Daniela Carrizales Sauceda, Regina A. Mangieri, Cole Maguire, and et al. 2026. "High-Dose Ethanol-Induced Immunosuppression Modulates Sex-Specific Disease Outcomes in a Murine Model of Multiple Sclerosis" Biomolecules 16, no. 3: 427. https://doi.org/10.3390/biom16030427

APA Style

Nuncio, A. S. P., Motovilov, K., Weed, M., Shah, S., Bazzi, S., Idnani, E., Lime, T., Sauceda, D. C., Mangieri, R. A., Maguire, C., & Melamed, E. (2026). High-Dose Ethanol-Induced Immunosuppression Modulates Sex-Specific Disease Outcomes in a Murine Model of Multiple Sclerosis. Biomolecules, 16(3), 427. https://doi.org/10.3390/biom16030427

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