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 ter m intranasal instillation of Penicillium chrysogenum propagules in a mouse model. Methods-C57 Black/6 mice were inoculated intranasally each week for six wee ks with 10(4) 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 10(4) P chrysogenum conidia (average viability 25%) produced significantly more total serum IgE (mean difference 1823.11, lower and upp er 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 neutro philia (mean difference 20.89, 95% CI 3.72 to 38.06), mice inoculated intra nasally with 10(4) non-viable conidia did not show significant changes in t otal serum IgE, peripheral or airway eosinophils. However, when compared wi th controls, this group (10(4) non-viable) had a significant increase in to tal serum IgG(1), (mean difference 1990.56, 95% CI 790.48 to 3190.63) and b ronchoalveolar lavage (BAL) fluid levels of interferon (IFN)-gamma (mean di fference 274.72, 95% CI 245.26 to 304.19). In addition, lung lavages from m ice inoculated intranasally with 10(4) viable P chrysogenum conidia had sig nificantly 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 2 1.99). The IgG(2a)/IgE ratio and the IFN-gamma/IL-4 ratio was lower in the group of mice inoculated intranasally with 10(4) viable conidia than in the 10(4) non-viable conidia group and the controls. When proteins were extrac ted from P chrysogenum conidia, attached to microtitre plates and incubated with serum from the 10(4) viable group, significant increases in conidia-s pecific IgE and IgG, were observed compared with controls, while serum from the 10(4) non-viable group was similar to controls. Conclusions-These data suggest that long term inhalation of viable P chryso genum propagules induces type 2 T helper cell mediated (Th2) inflammatory r esponses such as increases in total and conidia-specific serum IgE and IgG( 1), together with BAL fluid levels of IL-4 and IL-5 and peripheral and airw ay eosinophilia, which are mediators of allergic reactions.