Developing Natural Immunity To Asthma Caused By Research Rats

The findings appear in the first issue for July 2006 of the American Journal of Respiratory and Critical Care Medicine, published by the American Thoracic Society.

Meinir Jones, Ph.D., of the Department of Occupational and Environmental Medicine at Imperial College in London, and five associates analyzed the background information and blood tests of 689 pharmaceutical employees who had been exposed to lab rats in varying degrees.

The investigators wanted to learn more about the complex relationship between allergen exposure from the animals and the induction of human asthma. They noted that occupational asthma caused by an allergy to a laboratory animal can provide a useful model of allergic reaction from which exposure can be readily characterized and measured.

"We recorded the dates of their first and most recent handling of rats and estimated the duration of contact with rat proteins," said Dr. Jones. "Employees were classified according to the job they had that incurred the highest exposure to rats, with office and maintenance workers showing low exposure, scientists medium exposure, and animal technicians or cage cleaners high exposure."

There was close agreement between the exposure category associated with the job title and the maximum number of rats handled in one day.

"Approximately 38 percent had handled more than 50 rats per day, whereas 17 percent had never handled any," said Dr. Jones. "There were equal proportions, 23 and 22 percent, who had handled either from 1 to 10 or 11 to 50 rats. For 464 employees or 68 percent, their highest exposure to rat proteins came during their work as a scientist."

For the first time, the authors found a two-fold reduction in the risk of developing work-related chest symptoms in those who produced both rat-specific IgG4 and IgE antibodies, as compared with those producing IgE alone.

Immunoglobulin G (IgG) is one of five classes of immunoglobulins, which constitute the human body's main antibody defense against most bacterial invasions. Immunoglobulins also trigger antibodies against other antigens.

IgG is present primarily in human skin and mucus membranes. It functions in response to environmental challenges and plays a role in allergic reactions to those challenges.

"Laboratory animal workers may, at very high exposure, be experiencing a natural form of immunotherapy," said Dr. Jones. "Interestingly, this does not seem to be the case for other groups at risk of occupational asthma such as bakers and detergent manufacturers. We propose that the differences arise because laboratory animal workers experience exposure not only through inhalation but also through an intradermal route after bites and scratches."

In an editorial on the research in the same issue of the journal, Karin A. Pacheco, M.D., M.S.P.H., of the National Jewish Medical and Research Center in Denver, wrote: the authors "speculate that the protective effect against symptomatic disease offered by a high IgG4-IgE ratio reflects a form of natural immunotherapy."

"One of the strengths of the present manuscript is the categorization of exposure by the highest level, ever, of work with rats. This approach suggests that peak exposures are more important for the development of immune responses to laboratory animals than average exposures and acknowledges that exposure responsible for sensitization may have occurred in the past."