The immunobiology of early asthma.
What do we know? CD4+ T cells are strongly implicated in asthma pathogenesis. The "T(H)2 hypothesis" postulates two patterns of cytokine secretion by stimulated CD4+ T cells: a "T(H)1" response and a "T(H)2" response. T(H)2-type cytokines (interleukins IL-4, IL-5, IL-9, IL-13) regulate eosinophilia, mast cell growth, IgE and mucus production and have been proposed as key regulatory factors in asthma. T(H)1-type cytokines include interferon-gamma, IL-2, IL-12, IL-18, and tumour necrosis factor beta.T(H)2 responses are reciprocally inhibited by T(H)1 responses in animal models, but this may not be so in asthma in humans. In humans, T(H)1- and T(H)2-type cytokines are often coexpressed in early asthma. What do we need to know? Is cross-regulation between T(H)1 and T(H)2 immune biases truly lost in in early asthma? Can induction of T(H)1-type responses actually protect against asthma, as predicted by the "hygiene hypothesis"? If so, how might this induction be achieved safely in infants? Can the in-utero environment be subtly manipulated to minimise asthma risk? Does early childhood treatment with current anti-asthma drugs lead to long-term immune changes?
Anderson
Gary P
GP
Department of Medicine, University of Melbourne, Parkville, VIC. gpa@unimelb.edu.au
D000328:Adult; D000485:Allergens; D000818:Animals; D001249:Asthma / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D002648:Child; D002675:Child, Preschool; D016207:Cytokines / Q000276:immunology*; D006801:Humans; D007223:Infant; D013601:T-Lymphocytes / Q000276:immunology; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology*
D000485:Allergens; D016207:Cytokines