and specific aims): Asthma is characterized by airway obstruction, bronchial hyperresponsiveness, and persistent airway inflammation. Despite the accumulated data regarding the pathogenesis of asthma, relatively little is known about the role of cells which fundamentally control the immune response, and which regulate development and resolution of inflammation. Alveolar macrophages (AM) contribute to inflammation in asthma, via enhanced production of the inflammogenic factors granulocyte-macrophage colony stimulating factor (GM- CSF), and superoxide anion, or by impaired release of the antiinflammatory factor, interleukin (IL)-10. The application hypothesizes that impaired release of IL-10 by resident and recruited AM in asthma leads to persistent airway inflammation, and functional upregulation of AM.
The specific aims are: 1) to establish the capacity of unstimulated AM and monocytes of allergic asthmatics to produce IL-10 (and other relevant cytokines) at protein and mRNA levels, and to compare controls (allergic rhinitic [non-asthmatic] subjects, non-allergic asthmatics, and normal volunteers); 2) to establish the effects of segmental antigen challenge or segmental saline challenge on IL-10 production, at the protein and mRNA levels, by AM and monocytes of allergic asthmatics at several relevant times following challenge, and compare to controls; 3) to determine the functional consequences of AM to recombinant human [rh] GM-CSF and interferon (IFN)-g, or neutralizing antibodies to these factors, on AM production of IL-10; and 4) to determine the effects of exposure of AM to antibody against IL-10, and exogenous rhIL-10, using production of pro-inflammatory factors relevant to asthma (GM-CSF and superoxide anion) as indices.
| Calhoun, W J; Hinton, K L; Kratzenberg, J J (2001) The effect of salmeterol on markers of airway inflammation following segmental allergen challenge. Am J Respir Crit Care Med 163:881-6 |
