Got the Flu and Thinking of a Drink?... Why Your Liver Deteriorates Faster [Reading Science]

UNIST Identifies the Switch by Which Alcohol and Inflammation Kill Liver Cells
Suggests a New Drug Target for Intractable Liver Diseases

On days when you have a fever due to body aches or the flu, there is a common saying that "having a drink and sweating it out will help you recover." However, new scientific research shows that drinking alcohol in such cases may actually be much more harmful to your liver. For the first time, a Korean research team has revealed that when alcohol is consumed while the body's inflammatory response is already active, a so-called "immune overdrive switch" is triggered, causing liver cells to die much faster than usual.

The process by which interferon and alcohol induce cell death through ZBP1. When drinking alcohol in a state where interferon is secreted due to infection or inflammation, JNK signaling is activated, causing an abnormal increase in RNA (Z-RNA). The immune sensor ZBP1 detects this and triggers hepatocyte cell death. Additionally, alcohol reduces the production of the ADAR1 protein, which normally suppresses Z-RNA, thereby exacerbating liver damage. Provided by the research team

Professor Lee Sangjun's team from the Department of Biological Sciences at UNIST, in collaboration with Professor Rajendra Karki's team at Seoul National University and Professor Siming Ma's team at the Australian National University, announced on April 16 that they have uncovered the molecular mechanism by which alcohol and interferon (an inflammatory signal) combine to explosively induce hepatocyte cell death. The research findings have been published in the international journal Science Advances.

The key lies in the clash between the body's inflammatory signals and alcohol. When someone suffers from the flu, an infection, or severe inflammation, the immune system secretes interferon as a signaling molecule. If alcohol is consumed in this state, the amount of abnormal nucleic acid structures called Z-RNA increases rapidly in liver cells. The innate immune sensor ZBP1 (a protein that detects abnormal RNA in cells and activates inflammatory signaling) senses this, triggering a cell death response in hepatocytes.

Normally, a protein called ADAR1 (which processes abnormal RNA to prevent excessive immune reactions) conceals or modifies Z-RNA, preventing such immune overreactions. However, the research team found that alcohol partially inhibits the production of ADAR1 itself, making liver cells much more susceptible to inflammatory cell death.

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This study explains at the molecular level why drinking alcohol is particularly dangerous during the flu or other infectious diseases. It is not simply that the toxicity of alcohol damages the liver; rather, alcohol amplifies the immune response that is already active, creating a situation in which liver cells self-destruct.

The research team also verified these findings through animal experiments. When they inhibited the ZBP1 protein—which detects Z-RNA—in laboratory mice, there was a marked reduction in hepatocyte cell death and liver damage, even when both alcohol and interferon were present.

Research team photo. From left to right: Professor Lee Sangjun of UNIST, Researcher Oh Suhyun, Researcher Yoo Kyungjoo. Courtesy of UNIST

Furthermore, administering an inhibitor of the JNK (cell stress signaling pathway) also reduced liver damage. The study newly revealed that when alcohol and inflammation act together, the JNK pathway is activated, leading to the production of Z-RNA and the subsequent activation of ZBP1.

In other words, this research presents a new axis of liver injury: alcohol → interferon → JNK → Z-RNA → ZBP1. This is being evaluated as a new integrated model that goes beyond the conventional TLR4 and inflammasome pathways that have been central to explanations of alcoholic liver disease.

Professor Lee Sangjun stated, "Until now, the direct toxic effects of alcohol on liver cells have been considered the main cause of damage. However, we have demonstrated that alcohol-triggered immune responses can be another key mechanism driving hepatocyte cell death. This research lays the foundation for developing new therapeutics for alcoholic liver disease by targeting ZBP1."

This content was produced with the assistance of AI translation services.