Moderate Beer Intake Downregulates Inflammasome Pathway Gene Expression in Human Macrophages

SIMPLE SUMMARY: Moderate consumption of fermented beverages is associated with prevention against diseases involving inflammation and immunity. Conversely, for high drinking levels, an increase of inflammatory mediators and the susceptibility to infections occur, which tend to offset the benefits in terms of health. Unfortunately, this area remains poorly understood. Inflammation is now recognized as an overwhelming burden for public health. Thus, subcellular molecular complexes such as the “inflammasomes” have been identified as key players in cellular stress and tissue damage, and as regulators of immune and inflammatory responses. Here, we investigated the impact of moderate intake of alcohol-free and traditional beer in humans on the inflammasome pathway of activated pro-inflammatory human macrophages. The results of this study showed that macrophages submitted to a pro-inflammatory stimulus to activate the inflammosome had a mitigated inflammatory response in the presence of blood serum obtained from healthy volunteers after consuming alcohol-free or traditional beer for four weeks (women one can and men two cans per day) compared to the response found in the presence of blood serum obtained before beer intake. This was shown by a decrease in end components of the inflammasome cascade (IL-1β and TNF) at gene expression and protein level as found with alcohol-free and traditional beer, respectively. ABSTRACT: Inflammasomes are key components of the innate immunity system that trigger the inflammatory response. Inappropriate activity of the inflammasome system has been linked to onset and perpetuation of inflammation in atherosclerotic plaques and cardiovascular disease. Low-to-moderate beer consumption is inversely associated with cardiovascular event presentation, while high levels of alcohol intake are associated with increased cardiovascular risk. Although fermented beverages have been suggested to exert their beneficial effects through their anti-oxidant and anti-inflammatory properties, little is known regarding the capacity of beer to modulate innate immunity cell responses. To this aim, primed or activated THP-1 macrophages were conditioned with human serum obtained from a prospective two-arms longitudinal crossover study to investigate the effect of a moderate and regular daily intake of beer, either alcohol-free or traditional, in the regulation of TLR-mediated inflammatory responses in healthy but overweight individuals. Conditioned macrophages with serum obtained after four-week intervention with alcohol-free beer significantly reduced the transcription of pro-inflammatory interleukins such as IL-1β and TNF. The serum of traditional beer consumers did not exhibit the same capacity as the serum of alcohol-free beer consumers to reduce gene expression of pro-inflammatory interleukins; however, serum from traditional beer consumers showed a regulatory effect at the protein level by significantly decreasing the intracellular protein levels of pro-IL-1β in primed macrophages and preventing cleaved-IL-1β protein release.