Chapter

New Horizons in Allergy Immunotherapy

Volume 409 of the series Advances in Experimental Medicine and Biology pp 343-347

Role of Interleukin-4 in the Development of Allergic Airway Inflammation and Airway Hyperresponsiveness

  • M. Wills-KarpAffiliated withDepartment of Environmental Health Sciences, School of Hygiene and Public Health Johns Hopkins University
  • , S. H. GavettAffiliated withDepartment of Environmental Health Sciences, School of Hygiene and Public Health Johns Hopkins University
  • , Brian SchofieldAffiliated withDepartment of Environmental Health Sciences, School of Hygiene and Public Health Johns Hopkins University
  • , F. FinkelmanAffiliated withDepartment of Medicine, Uniformed Services University of the Health Sciences

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Abstract

Airway inflammation and airway hyperreactivity are consistent features of allergic asthma. The inflammatory response is characterized chiefly by an increase in eosinophils and T cells in bronchial mucosa and bronchoalveolar lavage fluids(1–5). Furthermore, as therapeutic interventions that reduce airway inflammation ameliorate airway hyperreactivity, inflammation is hypothesized to play a key role in the development of asthma-associated airway hyperreactivity(6,7). As a primary regulator of the inflammatory cascade, the T lymphocyte has been implicated in the pathogenesis of asthma(8). Considerable circumstantial evidence has been accumulating to support this hypothesis. For example, increased numbers of activated T cells are found in the bronchial mucosa of asthmatics as compared with control subjects(3). The degree of peripheral blood T lymphocyte activation correlates with the severity of asthmatic symptoms(9). In patients with allergic asthma, which is characterized as such by elevated serum IgE levels, allergen challenge induces a selective recruitment of CD4+ T cells into the airways(5). Moreover, the degree of activation of CD4+ lymphocytes correlates with the number of eosinophils in BAL fluid, with the degree of bronchial hyperreactivity, and with disease severity(10). CD4+ T cells isolated from bronchoalveolar fluids (BAL) of allergic asthmatics express increased levels of markers of acute and chronic activation(11). Such lymphocytes demonstrate a specific pattern of cytokine expression, namely, elevated levels of IL-4 and IL-5 mRNA, a pattern consistent with a T-helper 2 (TH2) pattern of differentiation(12) A possible immunopathogenic role for Th2 CD4+ T lymphocytes in asthma is suggested by the eosinophilia that characterizes asthma in general and the elevated IgE levels associated with allergic asthma.