Key Immune Substance Linked to Asthma

Reported July 25, 2011

(Ivanhoe Newswire) -- Nearly 28 million people in the United States have asthma. Asthma's signature symptom is extreme difficulty in breathing. It is accompanied by transient narrowing and long-term inflammation of the air passages and with time, lasting and detrimental structural changes in the architecture of the lungs. Researchers have now linked a master molecule of the immune system, gamma-interferon, to the pathology of asthma. The new study gathers evidence indicating that gamma-interferon may be contributing to the severity of asthma.

This finding is surprising since gamma-interferon has often been assumed to steer the immune system in a different direction from the cluster of allergic disorders to which asthma belongs, and could now lead to new treatments for the disease. The role of gamma interferon in asthma has been unclear.

"People thought gamma-interferon might have something to do with driving asthma's pathology, but there wasn't a whole lot of corroborating evidence," Stephen Galli, M.D., study author, and professor and chair of the Department of Pathology at Stanford Medical School, was quoted saying.

Gamma-interferon is a signaling molecule buried by certain immune cells. It mobilizes the immune system to fight infectious pathogens, or to attack healthy tissues, resulting in autoimmune disease. Asthma has been thought to result from a different mode of immune-system responses that battles multi-celled parasites such as intestinal worms, but can unfortunately also trigger allergic reactions.

The local abundance and activation in the lung tissue of immune cells called mast cells, is another prominent feature of asthma. Mast cells appear to be critical in the development of asthma. On their surfaces, these cells carry antibodies that bind to allergens such as cat dander, pollen, or cockroach droppings. This drives the mast cells to exude substances that trigger an asthma attack. Oddly, mast cells have receptors for gamma-interferon.
For the study, researchers used a mouse model of asthma to locate gamma-interferon's role in the disease. Mang Yu, M.D., Ph.D., a senior research scientist created the animal model of asthma. Five years ago, the researchers had reported on Yu's method for inducing asthma-like symptoms in healthy mice. The method involves repeatedly exposing the mice to a foreign substance over a period of 12 weeks.

During the 2006 study, the team used both Yu's asthma-inducing protocol and mast-cell-lacking mice to show that, as good as Yu's protocol may be at producing asthma-like features in normal mice, it loses its ability to do so in mast-cell-free mice. Providing those same mast-cell-lacking mice with healthy mast cells completely restored the protocol's capacity to induce asthma-like features. A similar approach in the new study which was to provide mast-cell-deficient mice with mast cells whose surface receptors for gamma interferon had been knocked out, showed a similar ability to reverse Yu's protocol's induction of asthma in the mice. Otherwise, giving fully functioning mast cells to such mice restored the protocol's power to trigger the asthma-associated symptoms and gene-activity level changes that normal mice develop under the treatment.

"This is potential important news, because it suggests that gamma-interferon might represent a therapeutic target," Dr. Galli said. However, "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. 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? We couldn't answer that question," Dr. Galli said.

"Even if levels of gamma-interferon are high in patients with severe asthma, that doesn't necessarily mean that if you block gamma-interferon they're going to get better. That would have to be established in clinical tests of human patients," Dr. Galli said.

The researchers plan to further study whether the findings observed in the mouse model actually apply to living, breathing, asthmatic human beings.

SOURCE: Journal of Clinical Investigation, July 5, 2011.