Alcohol Consumption in Rheumatoid Arthritis: A Path through the Immune System

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.

Alcohol-sourced acetate impairs T cell function by promoting cortactin acetylation

“…Here we hypothesized that the acetate’s inhibitory effect could be due to increased acetylation of the cytoskeletal proteins ultimately affecting T cell migration and function. Our hypothesis could explain alcohol’s double-edged sword effect in regard to benefits in autoimmunity and damages to health in general (Azizov and Zaiss, 2021; Schuckit, 2009). Alcohol consumption has correlated with decreased severity in rheumatoid arthritis, type 1 diabetes, SLE, and multiple sclerosis in humans as well as in disease mouse models (Azizov and Zaiss, 2021).…”

“…Our hypothesis could explain alcohol's double-edged sword effect in regard to benefits in autoimmunity and damages to health in general (Azizov and Zaiss, 2021;Schuckit, 2009). Alcohol consumption has correlated with decreased severity in rheumatoid arthritis, type 1 diabetes, SLE, and multiple sclerosis in humans as well as in disease mouse models (Azizov and Zaiss, 2021). Upon consumption, alcohol is rapidly metabolized to acetate contributing to increased serum concentrations (Zakhari, 2006).…”

“…Main Text: Multiple studies have shown detrimental effects of alcohol consumption on human health (1). In contrast, several clinical studies have demonstrated a correlation between autoimmune disease severity and moderate to high alcohol consumption (2). In an effort to better understand alcohol's effect on autoimmunity, we have shown that alcohol consumption mitigates T cell dependent humoral immune responses in preclinical rheumatoid arthritis (RA) and vaccination models (3).…”

Nutrition and Diet in Rheumatoid Arthritis

“…Alcohol consumption seems to exert effects on the efficacy of vaccinations but also induce protection against autoimmune diseases. In any case, the mechanism of alcohol's negative effects on the immune system is multivariate, as the authors conclude [10].…”

“…However, the amount of alcohol consumption becomes relevant in this regard. In their review in this Issue, Azizov et al report that heavy or moderate alcohol consumption can affect intestinal barrier integrity, as well as the gut microbiota, possibly contributing to RA [10].…”