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National Toxicology Program

National Toxicology Program

UPDATE NewsletterUPDATE NewsletterMay 2016

Mold exposures promote both allergic and inflammatory responses

By Kelly Lenox
Reprinted from Environmental Factor

The potential health effects of mold contamination in buildings are of growing concern, especially after the flooding associated with Hurricane Katrina and Superstorm Sandy. Scientists have moved one step closer to understanding these effects with a study that reported, for the first time, mechanisms associated with both allergic and inflammatory responses in the lungs of mice exposed to mold through inhalation.

The paper, published in the journal Clinical and Experimental Allergy, was made possible by innovative methods used in a collaboration between the National Toxicology Program (NTP) and one of its member agencies, the National Institute for Occupational Safety and Health (NIOSH). The findings have implications for treatment of illnesses associated with mold exposure.

Response triggered by germination of spores

Researchers found that after inhaling spores from the mold Aspergillus fumigatus, the lungs of mice developed significant adverse changes, linked with both allergic and inflammatory processes.

Germination of the mold appears to play a key role in the process. “Until now, there has been very limited evidence that germination is necessary for these responses,” said Dori Germolec, Ph.D., leader of the NTP Systems Toxicology Group. The project was conducted in collaboration with Ajay Nayak, Ph.D. and Brett Green, Ph.D., of the NIOSH Health Effects Laboratory Division (HELD), and Donald Beezhold, Ph.D., HELD director.

“We need to consider germination as an important component of potential toxicity when studying fungi,” Germolec stressed. “However, while we have found germination necessary for Aspergillus, it may not be necessary for all fungi,” she said. “Some, for example, have much larger conidia, which may not even get into the lung.” Conidia are fungal spores involved in reproduction.

Treatment should consider both allergy and inflammation

The findings have important implications for treatment of individuals living or working in moldy environments. “We now understand more about the kind of disease that can develop,” Germolec said. “The findings suggest that treatment should not target inflammation or allergy alone, but should consider both.”

Researchers found that animals that experienced subchronic exposure, which lasted 13 weeks, showed changes in the lungs consistent with the development of allergic responses, although the mice were not previously allergic. Cells in the lungs and airways experienced chronic inflammation and expressed a cytokine called interleukin-13, which is a hallmark of allergic response and plays a key role in allergic inflammation and airway diseases.

“This is a critical finding, as it demonstrates that a significant fraction of the T cells [immune response cells] that drive anti-fungal responses also contribute to the allergic outcomes,” the authors wrote.

“These results provide valuable insights for treatment of individuals exposed to moldy environments, whether a school, business, or home,” said Stavros Garantziotis, M.D., lead researcher for the NIEHS Natural History of Asthma with Longitudinal Environmental Sampling, or NHALES, study. He was not involved in the present research.

Innovative method overcomes earlier limitations

According to the authors, earlier studies were hampered by limited ability to control the dose of fungal particles, and by use of anesthesia in delivery of the substances. This team used a device, developed by NIOSH scientists, that can create and disperse dry mold spores at concentrations more like real-world human exposures.

NIOSH researchers previously used the device, an acoustical generator system, in studies of nanomaterials and silica. Its use in repeat dose toxicity studies for mold was tested and reported in the journal PLoS One in 2014.

Citation: Nayak AP, Green BJ, Lemons AR, Marshall NB, Goldsmith WT, Kashon ML, Anderson SE, Germolec DR, Beezhold DH 2016. Subchronic exposures to fungal bioaerosols promotes [sic] allergic pulmonary inflammation in naive mice. Clin Exp Allergy; doi:10.1111/cea.12724. [Online 19 Feb 2016]

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The Update Newsletter is produced by NTP Office of Policy, Review, and Outreach. The text is not copyrighted and can be reprinted without permission. If you use parts of the Update Newsletter in your publication, we ask that you provide us with a copy for our records. We welcome your comments and suggestions.

Director of Office of Policy, Review, and Outreach and Editor-in-Chief: Mary Wolfe | Managing Editor: Anna Lee Mosley