title: An animal model for allergic penicilliosis induced by the intranasal instillation of viable Penicillium chrysogenum conidia.
abstract: 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 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 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 10(4) non-viable conidia did not show significant changes in total serum IgE, peripheral or airway eosinophils. However, when compared with controls, this group (10(4) non-viable) had a significant increase in total serum IgG(2a) (mean difference 1990.56, 95% CI 790.48 to 3190.63) and bronchoalveolar lavage (BAL) fluid levels of interferon (IFN)-gamma (mean difference 274.72, 95% CI 245.26 to 304.19). In addition, lung lavages from mice inoculated intranasally with 10(4) 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 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 extracted from P chrysogenum conidia, attached to microtitre plates and incubated with serum from the 10(4) viable group, significant increases in conidia-specific IgE and IgG(1) 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 chrysogenum propagules induces type 2 T helper cell mediated (Th2) inflammatory responses 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 airway eosinophilia, which are mediators of allergic reactions.
authors.affiliation: Department of Microbiology and Immunology, Texas Tech University Health Sciences Center, Lubbock 79430, USA.
authors.forename: J D
authors.initials: JD
authors.lastname: Cooley
authors.forename: W C
authors.initials: WC
authors.lastname: Wong
authors.forename: C A
authors.initials: CA
authors.lastname: Jumper
authors.forename: J C
authors.initials: JC
authors.lastname: Hutson
authors.forename: H J
authors.initials: HJ
authors.lastname: Williams
authors.forename: C J
authors.initials: CJ
authors.lastname: Schwab
authors.forename: D C
authors.initials: DC
authors.lastname: Straus
mesh_terms: D000281:Administration, Intranasal; D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000276:immunology; D004804:Eosinophils / Q000276:immunology*; D005260:Female; D007073:Immunoglobulin E / Q000097:blood* / Q000276:immunology; D007074:Immunoglobulin G / Q000097:blood*; D007371:Interferon-gamma / Q000276:immunology; D015847:Interleukin-4 / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D010408:Penicillium chrysogenum / Q000276:immunology*; D018877:Sick Building Syndrome / Q000209:etiology; D013997:Time Factors
chemical_list: D007074:Immunoglobulin G; D015847:Interleukin-4; D007073:Immunoglobulin E; D007371:Interferon-gamma