Background: Animal models are used to mimic human asthma, however, not all models replicate the major characteristics of the human disease. Spontaneous development of asthma with hallmark features similar to humans has been documented to occur with relative frequency in only one animal species, the cat. We hypothesized that we could develop an experimental model of feline asthma using clinically relevant aeroallergens identified from cases of naturally developing feline asthma, and characterize immunologic, physiologic, and pathologic changes over 1 year. Methods: House dust mite (HDMA) and Bermuda grass (BGA) allergen were selected by screening 10 privately owned pet cats with spontaneous asthma using a serum allergen-specific IgE ELISA. Parenteral sensitization and aerosol challenges were used to replicate the naturally developing disease in research cats. The asthmatic phenotype was characterized using intradermal skin testing, serum allergen-specific IgE ELISA, serum and bronchoalveolar lavage fluid (BALF) IgG and IgA ELISAs, airway hyperresponsiveness testing, BALF cytology, cytokine profiles using TaqMan PCR, and histopathologic evaluation. Results: Sensitization with HDMA or BGA in cats led to allergen-specific IgE production, allergen-specific serum and BALF IgG and IgA production, airway hyperreactivity, airway eosinophilia, an acute T helper 2 cytokine profile in peripheral blood mononuclear cells and BALF cells, and histologic evidence of airway remodeling. Conclusions: Using clinically relevant aeroallergens to sensitize and challenge the cat provides an additional animal model to study the immunopathophysiologic mechanisms of allergic asthma. Chronic exposure to allergen in the cat leads to a variety of immunologic, physiologic, and pathologic changes that mimic the features seen in human asthma.

Tattersfield A, Knox A, Britton J, Hall I: Asthma. Lancet 2002;360:1313–1322.
Redd S: Asthma in the United States: Burden and Current Theories. Environ Health Perspect 2002;110(suppl 4):557–560.
Padrid P: Animal models of asthma; in Liggett SB, Meyers DA (eds): The Genetics of Asthma: Lung Biology in Health and Disease. New York, Dekker, 1995, pp 211–233.
Schelegle E, Gershwin L, Miller L, Fanucchi M: Allergic asthma induced in rhesus monkeys by house dust mite (Dermatophagoides farinae). Am J Pathol 2001;158:333–341.
Padrid P, Snook S, Finucane T: Persistent airway hyperresponsiveness and histologic alterations after chronic antigen challenge in cats. Am J Respir Crit Care Med 1995;151:184–193.
Moise N, Weidenkeller D, Yeager A: Clinical, radiographic, and bronchial cytologic features of cats with bronchial disease: 65 cases (1980–1986). J Am Vet Med Assoc 1989;194:1467–1473.
Guidelines for the Diagnosis and Management of Asthma, ed 2. Bethesda, National Institutes of Health, 1997, pp 1–153.
Dye J, McKiernan B, Rozanski E, Hoffmann W: Bronchopulmonary disease in the cat: Historical, physical, radiographic, clinicopathologic, and pulmonary function evaluation of 24 affected and 15 healthy cats. J Vet Intern Med 1996;10:385–400.
Talbott M, Strausser H: Increase in serum IgE levels of ovalbumin-sensitized cats and the detection of elastase and collagenase activities in secretions of sensitized feline alveolar macrophages challenged in vitro. Int Arch Allergy Appl Immunol 1977;54:198–204.
Norris C, Gershwin L, Decile K, Berghaus L: Cysteinyl leukotrienes in urine and bronchoalveolar lavage fluid in an experimental model of feline asthma. Am J Vet Res 2003;64:1449–1453.
Norris C, Decile K, Byerly J, Berghaus R, Schelegle E, Hyde D, Gershwin L: Production of polyclonal antisera against feline immunoglobulin E and its use in an ELISA in cats with experimentally induced asthma. Vet Immunol Immunopathol 2003;96:149–157.
Norris C, Byerly J, Decile K, Berghaus R, Walby W, Schelegle E, Hyde D, Gershwin L: Allergen-specific IgG and IgA in serum and bronchoalveolar lavage fluid in a model of experimental feline asthma. Vet Immunol Immunopathol 2003;96:119–127.
Foley J, Rand C, Leutenegger C: Inflammation and changes in cytokine levels in neurological feline infectious peritonitis. J Feline Med Surg 2003;5:313–322.
Leutenegger C, Mislin C, Sigrist B, Ehrengruber M, Hofmann-Lehmann R, Lutz H: Quantitative real-time PCR for the measurement of feline cytokine mRNA. Vet Immunol Immunopathol 1999;71:291–305.
Tournoy K, Kips J, Schou C, Pauwels R: Airway eosinophilia is not a requirement for allergen-induced airway hyperresponsiveness. Clin Exp Allergy 2000;30:79–85.
Cookson W: The alliance of genes and environment in asthma and allergy. Nature 1999;402S:B5–B11.
Kumar R, Foster P: Murine model of chronic human asthma. Immunol Cell Biol 2001;79:141–144.
St George J: Cell populations and structure-function relationships of cells in the airways; in Grardner D, Crapo J, Massaro J (eds): Toxicology of the Lung. New York, Raven Press, 1988, pp 71–101.
Kumar R, Foster P: Modeling allergic asthma in mice: Pitfalls and opportunities. Am J Respir Cell Mol Biol 2002;27:267–272.
Nilsson L, Gruber C, Granstrom M, Bjorksten B, Kjellman N: Pertussis IgE and atopic disease. Allergy 1998;53:1195–1201.
Dong W, Selgrade M, Gilmour M: Systemic administration of Bordetella pertussis enhances pulmonary sensitization to house dust mite in juvenile rats. Toxicol Sci 2003;72:113–121.
Djurup R: The subclass nature and clinical significance of the IgG antibody response in patients undergoing allergen-specific immunotherapy. Allergy 1985;40:469–486.
Arnaboldi P, Metzger D: The role of IgA in allergic lung inflammation. Keystone Symposia: Rethinking the Pathogenesis of Asthma, Santa Fe, 2002, p 47.
Bottcher M, Haggstrom P, Bjorksten B, Jenmalm M: Total and allergen-specific immunoglobulin A levels in saliva in relation to the development of allergy in infants up to 2 years of age. Clin Exp Allergy 2002;32:1293–1298.
Van der Zee J, Aalberse R: The role of IgG in immediate-type hypersensitivity. Eur Respir J 1991;4(suppl 13):91s–96s.
Cohn L, Ray A: T-helper type 2 cell-directed therapy for asthma. Pharmacol Ther 2000;88:187–196.
Spicuzza L, Polosa R: The role of adenosine as a novel bronchoprovocant in asthma. Curr Opin Immunol 2003;3:65–69.
Holgate S: The epidemic of allergy and asthma. Nature 1999;402S:B2–B4.
Van Rijt L, Lambrecht B: Role of dendritic cells and Th2 lymphocytes in asthma: Lessons from eosinophilic airway inflammation in the mouse. Microsc Res Tech 2001;53:256–272.
van Rensen E, Stirling R, Scheerens J, Staples K, Sterk P, Barnes P, Chung K: Evidence for systemic rather than pulmonary effects of interleukin-5 administration in asthma. Thorax 2001;56:935–940.
Leckie M, ten Brinke A, Khan J, Diamant Z, O’Connor B, Walls C: Effects of an interleukin-5 blocking monoclonal antibody on eosinophils, airway hyperresponsiveness, and the late asthmatic response. Lancet 2000;356:2144–2148.
Buttner C, Lun A, Splettstoesser T, Kunkel G, Renz H: Monoclonal anti-interleukin-5 treatment suppresses eosinophil but not T-cell functions. Eur Respir J 2003;21:799–803.
Pauwels R, Brusselle G, Kips J: Cytokine manipulation in animal models of asthma. Am J Respir Crit Care Med 1997;156:S78–S81.
Foster P, Ming Y, Matthei K, Young I, Temelkovski J, Kumar R: Dissociation of inflammatory and epithelial responses in a murine model of chronic asthma. Lab Invest 2000;80:655–662.
Davies D, Wicks J, Powell R, Puddicombe S, Holgate S: Airway remodeling in asthma: New insights. J Allergy Clin Immunol 2003;111:215–225.
Hamid Q: Images in allergy and immunology. J Allergy Clin Immunol 2003;111:431–432.
Fernandes D, Xu K, Stewart A: Anti-remodeling drugs for the treatment of asthma: Requirement for animal models of airway wall remodelling. Clin Exp Pharmacol Physiol 2001;28:619–629.
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