Effect of ageing on pulmonary inflammation, airway hyperresponsiveness and T and B cell responses in antigen-sensitized and -challenged mice.
BACKGROUND
The effect of ageing on several pathologic features of allergic asthma (pulmonary inflammation, eosinophilia, mucus hypersecretion), and their relationship with airway hyperresponsiveness (AHR) is not well characterized.


OBJECTIVE
To evaluate lung inflammation, mucus metaplasia and AHR in relationship with age in murine models of allergic asthma comparing young and older mice.


METHODS
Young (6 weeks) and older (6, 12, 18 months) BALB/c mice were sensitized and challenged with ovalbumin (OVA). AHR and bronchoalveolar fluid (BALF), total inflammatory cell count and differential were measured. To evaluate mucus metaplasia, quantitative PCR for the major airway mucin-associated gene, MUC-5AC, from lung tissue was measured, and lung tissue sections stained with periodic acid-Schiff (PAS) for goblet-cell enumeration. Lung tissue cytokine gene expression was determined by quantitative PCR, and systemic cytokine protein levels by ELISA from spleen-cell cultures. Antigen-specific serum IgE was determined by ELISA.


RESULTS
AHR developed in both aged and young OVA-sensitized/challenged mice (OVA mice), and was more significantly increased in young OVA mice than in aged OVA mice. However, BALF eosinophil numbers were significantly higher, and lung histology showed greater inflammation in aged OVA mice than in young OVA mice. MUC-5AC expression and numbers of PAS+ staining bronchial epithelial cells were significantly increased in the aged OVA mice. All aged OVA mice had increased IL-5 and IFN-gamma mRNA expression in the lung and IL-5 and IFN-gamma protein levels from spleen cell cultures compared with young OVA mice. OVA-IgE was elevated to a greater extent in aged OVA mice.


CONCLUSIONS
Although pulmonary inflammation and mucus metaplasia after antigen sensitization/challenge occurred to a greater degree in older mice, the increase in AHR was significantly less compared with younger OVA mice. Antigen treatment produced a unique cytokine profile in older mice (elevated IFN-gamma and IL-5) compared with young mice (elevated IL-4 and IL-13). Thus, the airway response to inflammation is lessened in ageing animals, and may represent age-associated events leading to different phenotypes in response to antigen provocation.
Busse
Paula J
PJ
Department of Medicine, Division of Clinical Immunology, Mount Sinai School of Medicine, New York, NY, USA. paula.busse@mssm.edu
Zhang
Teng Fei
TF
Srivastava
Kamal
K
Schofield
Brian
B
Li
Xiu-Min
XM
D000375:Aging / Q000276:immunology*; D000818:Animals; D001249:Asthma / Q000276:immunology / Q000503:physiopathology; D001402:B-Lymphocytes / Q000276:immunology; D016535:Bronchial Hyperreactivity / Q000139:chemically induced / Q000276:immunology*; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology* / Q000276:immunology; D004797:Enzyme-Linked Immunosorbent Assay; D004802:Eosinophilia / Q000276:immunology; D005260:Female; D015870:Gene Expression; D007371:Interferon-gamma / Q000096:biosynthesis; D018793:Interleukin-13 / Q000096:biosynthesis; D015847:Interleukin-4 / Q000096:biosynthesis; D015848:Interleukin-5 / Q000096:biosynthesis; D008679:Metaplasia; D051379:Mice; D008807:Mice, Inbred BALB C; D055271:Mucin 5AC; D009077:Mucins / Q000096:biosynthesis; D009093:Mucus / Q000276:immunology; D010047:Ovalbumin / Q000009:adverse effects; D011014:Pneumonia / Q000276:immunology* / Q000473:pathology; D016133:Polymerase Chain Reaction; D013601:T-Lymphocytes / Q000276:immunology
D018793:Interleukin-13; D015848:Interleukin-5; C524679:Muc5ac protein, mouse; D055271:Mucin 5AC; D009077:Mucins; D015847:Interleukin-4; D007371:Interferon-gamma; D010047:Ovalbumin