An animal model for allergic penicilliosis induced by the intranasal instillation of viable Penicillium chrysogenum conidia

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 104 P 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 viableP 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 chrysogenumconidia, 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.