Background and objective: Previous studies have suggested that quantitative differences in TH2-type cytokine responses in the airways are of particular importance in the pathogenesis of asthma. In this study we investigated whether alveolar macrophages (AMs) and peripheral blood monocytes (PMNs) are able to significantly influence the profiles of allergen-induced TH1 (IFN-gamma) and TH2 (IL-4 and IL-5) cytokine production by CD4+ T cells in atopic asthmatic subjects versus atopic nonasthmatic subjects and nonatopic normal subjects.
Methods: Peripheral blood CD4+ T cells were cultured alone or cocultured with either PMNs or AMs with allergen stimulation in the 3 groups.
Results: Although allergen stimulation did not change TH1 or TH2 cytokine responses in cultures of CD4+ T cells alone, the addition of PMNs to the cultures induced a significant increase in production of IL-4, IL-5, and IFN-gamma (P < .01 or P < .001) in atopic asthmatic subjects and atopic nonasthmatic subjects. However, PMNs induced a significant increase for IFN-gamma (P < .05) only in normal subjects. AMs from atopic asthmatic subjects significantly enhanced production of all 3 cytokines (P < .01 or P < .001), whereas the AMs from atopic nonasthmatic subjects significantly increased only production of IL-4 (P < .01) and IFN-gamma (P < .05) but not IL-5. Furthermore, IL-4 (P = .066) and IL-5 (P < .01) production in allergen-stimulated AM-CD4+ cell cocultures was higher in atopic asthmatic subjects but significantly lower in atopic nonasthmatic subjects (P < .05) as compared with the PMN-cocultures. For IFN-gamma, no difference was found between the AM and PMN cocultures in either atopic group. Allergen-stimulated IL-5 production in coculture with both AMs and PMNs inversely correlated with both baseline FEV1 percent predicted and PD20 methacholine in atopic asthmatic subjects (P < .05, P < .01, or P < .001).
Conclusion: These data suggest that AMs from atopic asthmatic subjects but not atopic nonasthmatic subjects, play a significant role in airway pathogenic immunity through enhancing TH2-type cytokine production.