The role of Penicillium chrysogenum conidia in Sick Building Syndrome and an asthma-like animal model

Abstract

Sick building syndrome (SBS) is a commonly used term for symptoms resulting from indoor air quality (lAQ) problems and has proven difficult to define. Complaints common to SBS include allergic rhinitis, difficulty in breathing, headaches, flu-like symptoms, and watering of the eyes. While fungal spores are now generally recognized as important causes of respiratory allergies, there are few studies showing which fungi and spores are associated with lAQ problems. Little is known about the role of fungal propagules in the pathogenesis of allergic diseases. These allergic reactions appear to result from the inhalation of fungal products, but the mechanism(s) responsible for these phenomena remain unclear.

In this study, we present evidence that PeniciUium species, especially PeniciUium chrxsogenum, are strongly associated with the occurrence of SBS in public schools. In addition, our deposition, clearance, and retention studies demonstrated that a significant number of P. chrxsogemim conidia that were introduced intranasally (IN) in a murine model were retained in the airways and remained viable for up to 36 h post-inoculation. Similar acute doses of viable conidia induced significant {P<0.001) increases in tumor necrosis factor a (TNF-a), while non-viable (NV) conidia did not.

In addition, the data demonstrated that mice inoculated intranasally (IN) weekly for 6 weeks with 10"^ P. chrysogenum conidia (average viability 257r) produced significantly increased amounts of total serum IgE (P=0.017), peripheral eosinophils (P=0.001), and airway eosinophiha (P=0.01) along with an increase in the number of airway neutrophils (P=0.059). Mice inoculated IN with lO"* NV conidia did not demonstrate significant changes in serum IgE, and peripheral or airway eosinophils. In addition, lung lavages from mice inoculated IN with 10** viable P. chnsogenum conidia demonstrated significant increases in interleukin 4 (IL-4) (P=0.015). and interleukin 5 (IL-5) (P=0.004).

These data suggest that long-term inhalation of viable P. chrxsogemim propagules induces inflammatory responses, such as increases in serum IgE. IL-4. And IL-5, along with peripheral and airway eosinophilia and airway neutrophilia, which are mediators of allergic reactions. The results also suggest that viable P. chnsogenum conidia may be producing a substance that is necessary to induce these responses.