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UI researchers study why some are protected from farmer's lung

IOWA CITY, Iowa -- Repeated exposure to molds often found in damp hay and grain can irritate the lungs causing a disease known as farmer's lung or hypersensitivity pneumonitis. The syndrome causes coughing and shortness of breath and is "reasonably common in the Midwest," says Dr. Gary Hunninghake, University of Iowa professor of internal medicine, who has studied the disease for many years.

People do not need to be in direct contact with hay or grain to be exposed to the molds, Hunninghake notes. The spores travel in the air and can settle in air conditioners and car air-cooling systems.

Activation of the immune system is necessary for the development of farmer's lung, and many people exposed to the molds develop antibodies; however, not everyone gets the disease. Only 10 to 15 percent of the people exposed to the molds get farmer's lung, while others get asthma or are unaffected.

The cause of this varied response to the molds remains elusive. It is one of the puzzles of the disease Hunninghake would like to solve.

He and co-investigator, Dr. Gunnar Gudmundsson, also in the department of internal medicine, moved a step closer to that goal when they identified a specific immune system protein, interferon-gamma, that is necessary for the development of hypersensitivity pneumonitis. These findings were reported in the May 15 issue of the Journal of Clinical Investigation.

Interferon-gamma is present in all humans and is one of three types of interferon. The others are interferon-alpha and interferon-beta.

Hunninghake and Gudmundsson found that mice genetically altered to have no interferon-gamma did not develop hypersensitivity pneumonitis after repeated exposure to the molds, while mice with the protein did develop the disease. Further, when interferon-gamma was replaced in the mice lacking the protein, they too developed farmer's lung after repeated exposure to the mold.

The fact that immune system activity is necessary to develop the disease did not surprise Hunninghake. He says it is common that hypersensitivity pneumonitis develops when immune system activity is increased, for example, following a cold. As an analogy, he notes that asthma is often worse after a viral infection.

These findings set the stage for further investigation into the factors that protect some people and not others from developing farmer's lung. Hunninghake believes the answer may be found in a complex combination of genetic makeup, degree of exposure to the mold and activity level of the immune system.

"When we get the riddles worked out in the animals, we'll move on to the patient studies," Hunninghake says. "When you test this in people, you want to know what you're looking for."