Molecular concepts of IgE-initiated inflammation in atopic and nonatopic asthma.
Atopic and nonatopic (intrinsic) asthmatics were characterized by a broadly conserved bronchial mucosal proeosinophilic cytokine network in which IL-5 appears to play a key role. Inappropriate IgE-mediated mechanisms may occur in asthma, irrespective of its atopic status, as suggested by elevated serum IgE concentrations and bronchial mucosal expression of FcepsilonRI, IL-4, IL-13, Iepsilon, and Cepsilon. In general, these observations support the concept that these subtypes of asthma, despite showing distinct clinical and biologic features, share many common immunopathologic mechanisms. The most promising future directions of research regarding intrinsic asthma concern the possible identification of novel allergens or antigens, the detailed description of local bronchial mucosal IgE production, and the understanding of a possible macrophage dysfunction. Furthermore, a role for infectious (viral?) or autoimmune processes has yet to be firmly identified in intrinsic asthma. Animal models may also help us to understand the role of IgE and atopy in asthma. Although these are largely IgE-mediated mechanisms, allergen-induced bronchial hyperresponsiveness and eosinophilic inflammation can also occur in the absence of IgE (null mutation of the Cepsilon locus), as shown in a mouse model of hypersensitivity to Aspergillus fumigatus (57). Thus, despite the absence of atopy, IgE-mediated mechanisms may operate in intrinsic asthma (Fig. 1).
Menz
G
G
Hochgebirgsklinik Davos-Wolfgang, Switzerland.
Ying
S
S
Durham
S R
SR
Corrigan
C J
CJ
Robinson
D S
DS
Hamid
Q
Q
Pfister
R
R
Humbert
M
M
Kay
A B
AB
D000818:Animals; D001249:Asthma / Q000276:immunology* / Q000473:pathology; D001980:Bronchi / Q000473:pathology; D018925:Chemokines / Q000502:physiology; D016207:Cytokines / Q000502:physiology; D006801:Humans; D006969:Hypersensitivity, Immediate / Q000276:immunology* / Q000473:pathology; D007073:Immunoglobulin E / Q000276:immunology*; D007249:Inflammation; D007378:Interleukins / Q000502:physiology; D008264:Macrophages / Q000276:immunology
D018925:Chemokines; D016207:Cytokines; D007378:Interleukins; D007073:Immunoglobulin E