Abstract
There is increasing evidence to suggest a key role for interleukin-5 (IL-5) in the regulation of airway eosinophilia in asthma. We compared the capacity for IL-5 production in atopic asthmatic, nonatopic asthmatic, atopic nonasthmatic and normal subjects, and evaluated the usefulness of peripheral blood cells for reflecting airway cell reactivity. Bronchoalveolar lavage (BAL) cells and peripheral blood mononuclear cells (PBMC) from 12 atopic and 10 nonatopic asthmatics (without inhaled steroid therapy), 9 atopic nonasthmatics, and 10 normal controls were cultured with or without house dust mite (HDM, 10 microg x mL-1) stimulation. CD4+ T-cell activation, IL-5 and interferon-gamma (IFN-gamma) production in the cultures were assessed. Both for BAL and PBMC samples, atopic and nonatopic asthmatic subjects showed comparable spontaneous production of IL-5, which was significantly higher than that either for atopic nonasthmatics or normal controls (p<0.05 or p<0.01). There was a significant correlation between the percentage of eosinophils in BAL and spontaneous production of IL-5 by BAL cells in both asthmatic groups (p<0.05 or p<0.01). Both these parameters were also associated with asthmatic airway narrowing as denoted by a negative relationship with baseline forced expiratory volume in one second (FEV1) as percentage predicted (p<0.05 and p<0.01, respectively). In contrast, IFN-gamma production by unstimulated BAL cells from normal controls was higher than that for BAL cell cultures of nonatopic asthmatic subjects (p<0.05). Following HDM stimulation, both atopic groups had comparable positive responses in terms of CD4+ T-cell activation, but there was relatively greater IL-5 production in asthmatic PBMC (p<0.05) and, in particular, BAL cell cultures (p<0.01). These findings suggest that elevated IL-5 production is a common feature of BAL cells and PBMC in atopic and nonatopic asthma. In addition, atopic asthmatics show greater IL-5 production in response to specific allergen compared with atopic nonasthmatics, an effect most marked in BAL cells compared to PBMC. Hence, peripheral blood mononuclear cells can reflect cytokine immunoreactivity of airway cells, but lack local cellular interactions, which limits their usage in asthma research.
