New-found protein may spur hunt for meds to treat sepsis, other inflammation

The life-threatening disease sepsis occurs when the body’s immune system launches an overly aggressive inflammatory response to a blood infection. It’s just one of several illnesses marked by overblown inflammation. But what causes that inflammation?

Scientists at the University of Illinois at Chicago believe they’ve identified a protein that’s key to triggering inflammation. The discovery could pave the way for the development of new drugs to tamp down massive inflammatory responses like those seen in sepsis.

The protein is called TWIK2, and it serves to transport potassium ions across cell membranes. That potassium passage across the TWIK2 channel activates structures inside immune cells, which in turn causes inflammation.

“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 and reduce inflammation,” said lead author Asrar Malik, Ph.D., professor and head of pharmacology in the UIC College of Medicine, in a statement.

The UIC team studied mouse models of sepsis and discovered that animals lacking TWIK2 had reduced levels of inflammation. They took macrophages—immune cells vital for fighting infections and cleaning up debris caused by inflammation—eliminated TWIK2 from them, and transplanted them into the mice. That prevented lung injury from inflammation, the researchers reported in the journal Immunity.

There are no drugs on the market directly targeting TWIK2, the researchers noted. However, the malaria treatment quinine does inhibit the functioning of TWIK2 in macrophages. They discovered that quinine cuts down on levels of interleukin 1-beta, a protein that causes fever.

There are many inflammatory diseases for which this discovery could be relevant, most notably sepsis. The disease affects about 1.7 million American adults a year, the Centers for Disease Control estimates, and it can become resistant to antibiotics. That’s why many of the research efforts aimed at combating sepsis are centered around finding new ways to kill the bugs that cause it. Last month, for example, scientists at Tufts University released research showing that one of the bacteria that causes sepsis, Acinetobacter baumannii, resists antibiotics by building a protective capsule around itself. They described how a network of molecules activates certain genes that enable the protective shield to be built.

But targeting inflammation directly is another priority, and the UIC researchers believe their discovery could help in the development of better drugs for controlling overly aggressive inflammatory responses. “By discovering new components of the inflammation pathways, we hope to pave the way for new personalized anti-inflammatory drugs which minimize the side effects for patients,” said co-author Jalees Rehman, M.D., an associate professor of medicine and pharmacology in the UIC College of Medicine.

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