Inflammation: Old drug offers new hope

Understanding exactly how to control inflammation would be a major breakthrough for medicine. New research uncovers vital information about how it works and may open the door to new treatments.

Inflammation is a double-edged sword. On one hand, it helps tissue to heal and protects it against further damage.

On the other hand, it can damage the very tissue it is meant to protect.

Many medical conditions involve inflammation, including heart disease, rheumatoid arthritis, asthma, and Crohn's disease.

It is for this reason that researchers are keen to unravel the complex pathways that lead to inflammation and cause it to overrun.

Among those interested in inflammation is a team of researchers from the University of Illinois at Chicago. Led by Prof. Asrar Malik, their latest results were published recently in the journal Immunity.

Inflammation and ions

For some time now, researchers have understood that inflammation is reliant on the activation of the inflammasome within immune cells. This cellular structure is "switched on" by an influx of potassium ions.

The flow of ions is known to be pivotal, but exactly how they enter the cell was not understood — until now.

Prof. Malik and team identified a potassium receptor known as TWIK2. In particular, the scientists investigated the receptor's role within macrophages, which are multipurpose immune cells that clear up cellular debris during inflammation and attack pathogens.

To identify TWIK2 as a central player in the inflammation mechanism, they used a mouse model of sepsis. Sepsis is a life-threatening condition caused by a disproportionately large inflammatory response following an infection.

The team showed that mice that lack the TWIK2 receptor experience much less inflammation, and the inflammasomes are less active. They also found that when macrophages without TWIK2 were transplanted into mice whose macrophages had been removed, lung inflammation was reduced.

Understanding which receptor might be involved in inflammation is interesting in its own right, but the long-term implications are what really matters.

"Now that we have identified this crucial channel, it opens up the possibility of developing targeted new anti-inflammatory drugs to modify its function and help reduce inflammation."

Prof. Asrar Malik

New drugs from old molecules

Drugs that operate at potassium channels have already been designed, but none specifically target TWIK2. However, a potential starting point for research into new ways to influence this channel might be found in an old remedy: quinine.

Quinine — which is responsible for the bitter taste in tonic water — is a chemical found in cinchona bark. It has been used as an antimalarial and anti-inflammatory drug since the 18th century.

According to study co-author Dr. Jalees Rehman, "Some of the fever-suppressing effects of quinine may be due to its effects on the TWIK2 channel. We found that quinine reduced the levels of the inflammatory molecule interleukin 1-beta, which is known to cause fever."

Current anti-inflammatory medications tend to bring with them some unpleasant side effects, such as stomach ulcers, cardiovascular problems, and bowel perforations. So, finding something that acts in such a specific manner might help to design drugs with less harmful consequences.

Dr. Rehman hopes that their work will "pave the way for new personalized anti-inflammatory drugs, which minimize the side effects for patients."