Heavy alcohol consumption turns out to increase brain inflammation

Inflammation in critical areas of the brain could explain the risky decision-making we see in people with alcohol use disorder.
Sejal Sharma
Excessive drinking can cause brain inflammation.
Excessive drinking can cause brain inflammation.


Our nervous system regularly interacts with our immune system so that our bodies can fight against infection from pathogenic microorganisms and allow our nervous system to regulate immune functioning.

These neuroimmune interactions not only regulate the functioning of our brains, emotions, and mood but also play a role in several neuropsychiatric diseases, including alcohol use disorder (AUD).

Alcohol use disorder, in simple terms, is an abuse of alcohol, so much so that the person doesn’t stop drinking even when it causes problems. The person often goes into a negative emotional state. It may also lead to alcoholism.

A team of scientists has found a new link between how excessive drinking can cause inflammation in critical areas of the brain, which would potentially impact decision-making and impulsivity.

How alcohol dependence impacts brain activity

The researchers compared alcohol-dependent mice with another group of mice drinking moderate or no alcohol at all. They found that the signaling molecules in the immune system, which protect us against diseases and regulate the inflammatory response in bodies, are present at higher levels in the brain of mice with alcohol dependence. The signaling molecule they refer to here is called interleukin 1β (IL-1β).

In the group of mice which had been moderately or not exposed to alcohol at all, the IL-1β signals did their job properly and activated an anti-inflammatory signal pathway. 

However, the IL-1β pathway had an opposite reaction in the alcohol-dependent mice. Their brain activity saw pro-inflammatory signaling, likely contributing to changes in brain activity associated with AUD - like increasingly risky decision-making and impulsivity that drive further cycles of binge drinking as individuals transition to the dependent state.

Notably, these changes in IL-1β signaling persisted even during alcohol withdrawal.

It’s a vicious cycle between changes to the brain and changes to behavior.

While there already exists FDA approved drugs in the market to block high levels of IL-1β, senior author of the research Marisa Roberto, said, “We plan to follow up on this study with more work on exactly how targeting specific components of the IL-1β pathway might be useful in treating alcohol use disorder.”

This research, by the Scripps Research Institute, was published in the peer-reviewed journal Brain, Behavior, and Immunity.

Study abstract:

Neuroimmune pathways regulate brain function to influence complex behavior and play a role in several neuropsychiatric diseases, including alcohol use disorder (AUD). In particular, the interleukin-1 (IL-1) system has emerged as a key regulator of the brain’s response to ethanol (alcohol). Here we investigated the mechanisms underlying ethanol-induced neuroadaptation of IL-1β signaling at GABAergic synapses in the prelimbic region of the medial prefrontal cortex (mPFC), an area responsible for integrating contextual information to mediate conflicting motivational drives. We exposed C57BL/6J male mice to the chronic intermittent ethanol vapor-2 bottle choice paradigm (CIE-2BC) to induce ethanol dependence, and conducted ex vivo electrophysiology and molecular analyses. We found that the IL-1 system regulates basal mPFC function through its actions at inhibitory synapses on prelimbic layer 2/3 pyramidal neurons. IL-1β can selectively recruit either neuroprotective (PI3K/Akt) or pro-inflammatory (MyD88/p38 MAPK) mechanisms to produce opposing synaptic effects. In ethanol naïve conditions, there was a strong PI3K/Akt bias leading to a disinhibition of pyramidal neurons. Ethanol dependence produced opposite IL-1 effects - enhanced local inhibition via a switch in IL-1β signaling to the canonical pro-inflammatory MyD88 pathway. Ethanol dependence also increased cellular IL-1β in the mPFC, while decreasing expression of downstream effectors (Akt, p38 MAPK). Thus, IL-1β may represent a key neural substrate in ethanol-induced cortical dysfunction. As the IL-1 receptor antagonist (kineret) is already FDA-approved for other diseases, this work underscores the high therapeutic potential of IL-1 signaling/neuroimmune-based treatments for AUD.

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