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Asthma, gamma-interferon, and the mouse that didn't wheeze

In a just-out study, Stanford's Steve Galli, MD, Mang Yu, MD, PhD, and their colleagues induced a condition very closely mimicking asthma's molecular and cellular symptoms, not just the wheezing, in lab mice. But doing so required the active involvement of an intercellular signaling protein called gamma-interferon, they showed.

So it looks as though gamma-interferon may be a major player in the pathology of asthma. 

That's a surprise. Asthma, which affects almost 30 million people in the United States alone, is largely an allergic condition triggered by inappropriate arousal of an immune-response mode calibrated to combat multicellular parasites (try not to think about them). IFN-gamma, on the other hand, is best known for stimulating a competing mode of immune response, one that is more suited to fighting microbial infections (and, alas, for sometimes aiding and abetting autoimmune disease).

That 4-dimensional pinball game we call the "immune response" is always full of surprises.

Then again, this was in mice. Says Galli:

My MD doesn’t stand for "mouse doctor." It stands for ‘medical doctor.’ And I recognize that human asthma is not necessarily the same as a mouse model of asthma, even a very good one like the one we’re using. In implicating gamma-interferon as one of the drivers of pathology in this mouse model of asthma, we’ve raised just one question, which is: "Could this also be true in humans and, if so, might interfering with gamma-interferon be helpful in treating them?" Mang and I can work on mice until the cows come home, and we couldn’t answer that question.

Sally Wenzel, MD, director of the University of Pittsburgh Asthma Institute, has found suspiciously high levels of gamma-interferon in severe asthma patients' lungs. Wenzel intends to collaborate with Galli in human studies. If the mouse findings hold up, there could be significant therapeutic implications.

“The reason severe asthma exists is that some people don’t respond well to typical therapies,” Wenzel says. Stay tuned.

Photo by Maggiejumps

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