U. cardiologist discovers new possibility for treating arthritis, inflammation

By David Self Newlin | Posted - Nov 15th, 2012 @ 11:45am



SALT LAKE CITY — Sometimes your body needs to tear itself apart in order to heal. Anyone who has ever sprained their ankle or got an infection has seen that exact process happen: Swelling, redness, pain and all those familiar signs of injury.

For some people, though — folks with arthritis, inflammatory bowel disease or lupus — the body never stops doing this, leading to a lifetime of pain and sickness. Drugs used to treat them can be effective but are like dropping a bomb on the immune system, leading to the risk of infection or other complications.

University of Utah cardiologist Dr. Dean Li has discovered it may be possible to treat these diseases in a completely new way, one that would ease the pain of those who suffer from inflammatory disorders, but still protect the body's ability to protect itself.

"We're wondering whether we could conceive of a different way of thinking about how to treat this," Li said.

Creative destruction

When your body needs to fix itself after an injury, it releases complex molecules called cytokines. These proteins are released into the bloodstream and are responsible for activating an immune response, including white blood cells. They essentially tell the body to wake up and get to work fixing a perceived immune threat.

They also cause inflammation by damaging tissue.

"But they also begin to loosen the tissue architecture," Li said. "Your blood vessels, they don't quite fall apart. They become leakier."

This may seem counterintuitive, but by breaking down this structure, cytokines and other immune responses have a better shot of getting access to cells and taking out the threat, be it bacteria, virus or something else.

The body goes too far

The problem is that sometimes people's immune response is out of whack and these cytokines cause unnecessary inflammation and huge amounts of pain, the kind seen in arthritis or inflammatory bowel disease. Unchecked inflammation can be treated with antibody-based drugs like Remicade, but these come with their own downside, like depressing the body's entire immune system.

"Essentially, people with inflammatory diseases, what's happening is your immune system is so revved up and the way that we (treat it) is we take a gun and we blow up the immune system," Li said.

Folks undergoing treatment for inflammatory diseases are at a very high risk of catching something else because their immune system is shut down by the drug that treats inflammation. In addition, these antibody-based drugs have to be administered in an hospital regularly, making treatment difficult for patients who may already have trouble getting around.

So Li conducted a study and found that while the same cytokines cause both immune responses and inflammation, they do so using two distinct pathways in the body, something that had not been shown before. That means it's possible to create a treatment that blocks the cytokines' path to causing inflammation, but allows the immune system to function normally.

"We think your immune system is really important," Li said. "We just don't think your immune system should destroy everything in its path. And if we could selectively do that and not totally decimate the village of your immune system, we might do a little bit better."

It also means that it should be possible to create a small-molecule drug that could be administered in pill form, rather than forcing someone to come into the hospital for treatment.

The study was funded by the National Institutes of Health and was published in the journal Nature online.

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