Different profiles of T-cell IFN-gamma and IL-12 in allergen-induced early and dual responders with asthma.
BACKGROUND
IFN-gamma and IL-12 are anti-inflammatory cytokines released from various cells, including T cells. Allergen inhalation by atopic subjects with asthma results in 2 bronchoconstrictor phenotypes, termed isolated early and dual responders . Persistence of allergen-induced airway response and inflammation is a distinctive feature of dual responders.


OBJECTIVE
To evaluate the roles of IFN-gamma and IL-12 in resolving allergen-induced airway inflammation by comparing T lymphocytes (CD4 + and CD8 + cells) producing these cytokines in isolated early and dual responders.


METHODS
Twenty-four subjects with asthma (12 isolated early and 12 dual responders) were challenged with inhaled allergen. Peripheral blood and induced sputum were taken before and 1 day, 3 days, and 7 days after challenge. Frequency of IFN-gamma, IL-12, IL-4, and IL-13 producing CD4 + and CD8 + cells was assessed by using flow cytometry.


RESULTS
After allergen, both CD4 + and CD8 + IFN-gamma positive cells in peripheral blood significantly decreased in dual responders only, whereas CD4 + and CD8 + IFN-gamma positive cells in induced sputum significantly increased in isolated early responders only. By contrast, IL-12 positive cells in peripheral blood significantly increased after allergen challenge only in isolated early responders. The ratio of CD4 + and CD8 + IL-4/IFN-gamma positive cells in peripheral blood significantly decreased in isolated early responders by 3 days and had recovered by 7 days.


CONCLUSIONS
These results suggest that contrasting profiles of IFN-gamma and IL-12 production may be responsible for different time courses of allergen-induced airway responses between isolated early and dual responders.
Yoshida
Makoto
M
Firestone Institute for Respiratory Heath, Department of Medicine, McMaster University, Health Sciences Center, Ontario, Canada.
Watson
Richard M
RM
Rerecich
Tracy
T
O'Byrne
Paul M
PM
D000485:Allergens / Q000008:administration & dosage / Q000276:immunology; D001249:Asthma / Q000097:blood / Q000276:immunology*; D001985:Bronchial Provocation Tests; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D005434:Flow Cytometry; D006801:Humans; D007371:Interferon-gamma / Q000032:analysis / Q000096:biosynthesis*; D018664:Interleukin-12 / Q000032:analysis / Q000096:biosynthesis*; D018655:Lymphocyte Count; D016210:Methacholine Chloride; D013183:Sputum / Q000276:immunology; D013997:Time Factors
D000485:Allergens; D016210:Methacholine Chloride; D018664:Interleukin-12; D007371:Interferon-gamma