An anti-inflammatory molecule already approved by the U.S. Food and Drug Administration for autoimmune diseases was found to reduce excessive alcohol consumption in alcohol-dependent female mice, according to a Scripps Research study published on June 29.
The research, appearing in the Journal of Neuroinflammation on May 22, centers on interleukin-6 (IL-6), a molecule produced by the body during stress, infection, and injury. IL-6 is known for its role in inflammation related to diseases such as rheumatoid arthritis but is also produced by brain cells where it can influence neural circuits.
Previous studies indicated that heavy drinkers tend to have higher levels of IL-6 in their blood and that certain genetic variants of the IL-6 gene are linked with increased risk of alcohol use disorder. The research team led by Roberto explored whether blocking IL-6 could impact drinking behavior using a mouse model exhibiting compulsive drinking. They confirmed that chronic alcohol exposure raised IL-6 signaling within the central amygdala—a brain region associated with addiction behaviors—and found that IL-6 suppresses the GABA system there, which typically prevents overactivation of neurons.
"GABA is an important brake signal that the brain uses to dampen the activity of neurons," said Chloe Erikson, co-first author and postdoctoral fellow at Scripps Research. "When this braking system gets weakened, over-excitation can result. That loss of inhibitory control plays a large role in alcohol use disorder-associated behaviors like alcohol consumption, craving, and withdrawal."
Researchers administered an antibody targeting the IL-6 receptor—similar to drugs used for rheumatoid arthritis—to alcohol-dependent mice. Female mice treated with this antibody drank significantly less alcohol than before treatment; however, dependent males and non-dependent animals did not show significant changes. "In the human literature, we know that women are more prone to autoimmune diseases, so while the positive results in our female mice were surprising, they aligned with clinical data," said Celsey St. Onge, co-first author at Scripps Research.
The team also analyzed postmortem brain tissue from people diagnosed with alcohol use disorder and those without it; they identified 377 genes expressed differently between groups—with elevated levels of IL-6 among those with alcohol use disorder—supporting links between inflammation pathways and addiction behaviors.
Roberto said, "There has been a substantial shift in the field in the past few years to classify alcohol use disorder as a whole-body disease... It's our hope that classifying it as such can continue to destigmatize this complex disorder."
