Abstract
Benefits and harms of different components of human diet have been known for hundreds of years. Alcohol is one the highest consumed, abused, and addictive substances worldwide. Consequences of alcohol abuse are increased risks for diseases of the cardiovascular system, liver, and nervous system, as well as reduced immune system function. Paradoxically, alcohol has also been a consistent protective factor against the development of autoimmune diseases such as type 1 diabetes, multiple sclerosis, systemic lupus erythematosus, and rheumatoid arthritis (RA). Here, we focused on summarizing current findings on the effects of alcohol, as well as of its metabolites, acetaldehyde and acetate, on the immune system and RA. Heavy or moderate alcohol consumption can affect intestinal barrier integrity, as well as the microbiome, possibly contributing to RA. Additionally, systemic increase in acetate negatively affects humoral immune response, diminishing TFH cell as well as professional antigen-presenting cell (APC) function. Hence, alcohol consumption has profound effects on the efficacy of vaccinations, but also elicits protection against autoimmune diseases. The mechanism of alcohol’s negative effects on the immune system is multivariate. Future studies addressing alcohol and its metabolite acetate’s effect on individual components of the immune system remains crucial for our understanding and development of novel therapeutic pathways.
Highlights
It is first metabolized to acetaldehyde by alcohol dehydrogenase (ADH), acetaldehyde is metabolized to acetate by aldehyde dehydrogenase (ALDH) by various cells of the body
Measuring direct effects of alcohol in vivo can be challenging, one of the ways it is delineated from the effects of other metabolites of alcohol is by decreasing the time between alcohol administration and quantification of parameters
In the context of collagen-induced arthritis (CIA), alcohol-fed mice exhibited no significant changes to CD4+ T cell populations aside from reduced Treg cells in the spleens and dLNs [54]
Summary
Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations. Nutrition in general has been shown to have strong effects on autoimmunity; in a study of alcohol-use and SLE, there was a significant correlation of wine but not beer consumption as a protective factor [31,35]. Acetaldehyde, the first metabolite of alcohol, in alcoholic liver disease (ALD) patients has been shown to negatively affect tight junction molecules in intestinal epithelium, and cause increased serum LPS, which is correlated with. In our laboratory, we were able to show that modulation of intestinal tight junction can affect onset of RA in the preclinical collagen-induced arthritis (CIA) model of RA [40] Another metabolite of alcohol, acetate, is a central molecule in cellular metabolism, post-translational modifications, and transcription in its biologically active acetyl-CoA form [41]. We review known effects of alcohol and alcohol’s metabolites, acetaldehyde and acetate, on the immune system within the scope of autoimmunity, namely, RA
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