Anti-interleukin 5 but not anti-IgE prevents airway inflammation and airway hyperresponsiveness.
The role of IL-5 and allergen-specific IgE in the development of eosinophilic airway inflammation and airway hyperresponsiveness (AHR) was investigated in a murine model. BALB/c mice were sensitized to ovalbumin (OVA) by intraperitoneal injection on Days 1 and 14, followed by airway challenge with OVA on Days 28 and 29. Anti-IL-5 (TRFK-5) or anti-IgE (antibody 1-5) was administered before each airway challenge. Sensitized and challenged mice developed increased OVA-specific IgE serum levels, Th2 cytokine production by peribronchial lymph node (PBLN) cells, increased numbers of eosinophils (predominantly located in the peribronchial regions of the lungs), and increased airway responsiveness to methacholine (MCh). Anti-IgE treatment significantly decreased serum anti-OVA IgE levels and prevented the development of anaphylaxis but failed to affect T cell function, eosinophil airway infiltration, and AHR in sensitized and challenged mice. In contrast, treatment with anti-IL-5 antibody did not affect B cell (Ig serum levels), T cell (cytokine production), or mast cell function (immediate cutaneous reactivity) but completely inhibited development of eosinophilic lung inflammation and AHR. These data identify IL-5-mediated eosinophilia as a major target for development of AHR in this model, with little effect resulting from neutralization of IgE.
Hamelmann
E
E
Division of Basic Sciences, Department of Pediatrics, National Jewish Medical and Research Center, Denver, Colorado, USA.
Cieslewicz
G
G
Schwarze
J
J
Ishizuka
T
T
Joetham
A
A
Heusser
C
C
Gelfand
E W
EW
D000704:Analysis of Variance; D000818:Animals; D000906:Antibodies / Q000494:pharmacology; D016535:Bronchial Hyperreactivity / Q000276:immunology*; D018893:Bronchoalveolar Lavage; D002478:Cells, Cultured; D016207:Cytokines / Q000276:immunology; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D004804:Eosinophils / Q000276:immunology; D005260:Female; D007073:Immunoglobulin E / Q000276:immunology*; D007249:Inflammation; D015848:Interleukin-5 / Q000276:immunology*; D008168:Lung / Q000276:immunology* / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D010047:Ovalbumin / Q000276:immunology
D000906:Antibodies; D016207:Cytokines; D015848:Interleukin-5; D007073:Immunoglobulin E; D010047:Ovalbumin