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Background: Recent evidence has shown that viable conidia from the fungus Penicillium chrysogenum induce allergic effects in mice. The present study was conducted to determine the specific allergic dose response of C57BL/6 mice to the protease extract, Pen ch, isolated from viable P. chrysogenum conidia. Methods: Mice were treated with primary intraperitoneal (IP) injections of 10 or 100 μg of Pen ch adsorbed to alum, followed by weekly IP injections of 0.1, 1.0, or 10.0 μg Pen ch with alum for 4 weeks, and with 10.0 μg of Pen ch by intranasal (IN) inoculations the final 2 weeks before killing. Results: Intraperitoneal injections of 10 and 100 μg of Pen ch for 5 weeks followed by 2 weeks of IN instillation of 10 μg induced significant increases of total serum immunoglobulin (Ig)E and IgG1. Bronchoalveolar lavage cell counts revealed increased numbers of eosinophils and neutrophils. Histopathological examination of lungs detected perivascular inflammation by eosinophils and neutrophils and increased mucous production. Conclusions: The data presented in this study indicate that sensitization to protease allergens released by viable P. chrysogenum conidia in vivo induce a strong allergic inflammatory response in a murine model, which could have implications for people exposed to high levels of conidia of this organism.

Publisher Summary This chapter elucidates the role of fungi in the phenomenon of sick building syndrome (SBS). The most common symptoms of SBS are fatigue, runny nose, itchy eyes, sore throat, and headaches. Although no single cause for the above symptoms is likely to be found, the presence of certain molds is becoming increasingly associated with this phenomenon. Several studies suggest that the elevation of culturable Penicillium species conidia in the indoor air over the levels in the outside air causes health problems in human beings. The inhalation of Penicillium species conidia is associated with the initiation of an asthmatic attack. Alternaria species spores and Penicillium species conidia provoke immediate and delayed-type asthma in individuals already sensitized to these organisms. Penicillium species conidia tends to colonize the heating, ventilation, and air conditioning (HVAC) systems of buildings. There is one other important respiratory disease caused by the inhalation of Penicillium species conidia : cheese worker's lung or cheese washer's disease, an occupational disease.

BACKGROUND—A study was undertaken to determine the consequences of long term intranasal instillation of Penicillium chrysogenum propagules in a mouse model. METHODS—C57 Black/6 mice were inoculated intranasally each week for six weeks with 104 viable and non-viable P chrysogenum conidia. Cytokine levels and cellular responses in these animals were then measured. RESULTS—Compared with controls, mice inoculated intranasally each week for six weeks with 104P chrysogenum conidia (average viability 25%) produced significantly more total serum IgE (mean difference 1823.11, lower and upper 95% confidence intervals (CI) 539.09 to 3107.13), peripheral eosinophils (mean difference 5.11, 95% CI 2.24 to 7.99), and airway eosinophilia (rank difference 11.33, 95% CI 9.0 to 20.0). With the exception of airway neutrophilia (mean difference 20.89, 95% CI 3.72 to 38.06), mice inoculated intranasally with 104 non-viable conidia did not show significant changes in total serum IgE, peripheral or airway eosinophils. However, when compared with controls, this group (104 non-viable) had a significant increase in total serum IgG2a (mean difference 1990.56, 95% CI 790.48 to 3190.63) and bronchoalveolar lavage (BAL) fluid levels of interferon (IFN)-γ (mean difference 274.72, 95% CI 245.26 to 304.19). In addition, lung lavages from mice inoculated intranasally with 104 viable P chrysogenum conidia had significantly increased levels of interleukin (IL)-4 (mean difference 285.28, 95% CI 108.73 to 461.82) and IL-5 (mean difference 16.61, 95% CI 11.23 to 21.99). The IgG2a/IgE ratio and the IFN-γ/IL-4 ratio was lower in the group of mice inoculated intranasally with 104 viable conidia than in the 104 non-viable conidia group and the controls. When proteins were extracted from P chrysogenum conidia, attached to microtitre plates and incubated with serum from the 104 viable group, significant increases in conidia-specific IgE and IgG1 were observed compared with controls, while serum from the 104 non-viable group was similar to controls. CONCLUSIONS—These data suggest that long term inhalation of viable P chrysogenum propagules induces type 2 T helper cell mediated (Th2) inflammatory responses such as increases in total and conidia-specific serum IgE and IgG1, together with BAL fluid levels of IL-4 and IL-5 and peripheral and airway eosinophilia, which are mediators of allergic reactions.

Allergic reactions in recipients of Rift Valley fever vaccine (RVFV) are extremely rare. When vaccine was given by various routes to selected mouse strains, intraperitoneal (IP) priming of C3H/HeJ mice with RVFV resulted in acute respiratory arrest of all mice upon secondary IP inoculation on day 14. All C3H/HeJ mice given intranasal (IN) boost had distress but only 67% died. In contrast, no C3H/HeN mice died following re-exposure to RVFV vaccine. C3H/HeJ mice have high splenic IgA responses as shown by Kiyono et al. [1]. We examined commitment of local B-cells to IgA and IgE expression by Northern blot analysis of extracted RNA from tissues of control and RVFV immunized mice. Using the α660 cDNA probe we found increased α mRNA in lungs and spleens of C3H/HeJ, while there was decreased α mRNA in the same organs of C3H/HeN mice 14 days after IP immunization. Northern blots were also probed for e mRNA with the cDNA chimera, C230. Low levels of e mRNA were found in all tissues of control C3H/HeN mice. Immunization resulted in differences in e mRNA levels consistent with association of locally-produced IgE with respiratory allergy in C3H/HeJ mice.

C3H/HeJ mice, which are non-responsive to lipopolysaccharide (LPS), elicit higher IgA responses, including increased splenic indirect plaque-forming cell and serum antibody responses to orally administered antigen compared to the syngeneic LPS responsive C3H/HeN mice (1). These elevated IgA responses are thought to be due to induction of T helper cell activity in mucosal lymphoid tissue (2).