Modulatory effects of alveolar macrophages on CD4+T-cell IL-5 responses correlate with IL-1 beta, IL-6, and IL-12 production

Increasing evidence suggests that the pattern of T-cell cytokine production can be modulated by antigen presenting cell (APC)-derived factors during t he cell interactions. Recently, it has been shown that alveolar macrophages (AMs) from atopic asthmatics (AA) but not atopic nonasthmatics (AN) enhanc e interleukin (IL)-5 production by CD4+ T-cells. The present study compared AM production of IL-1 beta, IL-6, and IL-12, as well as their associated functional capacity to influence IL-5 production b y allergen-specific CD4+ T-cells in 10 AA, 10 AN, and nine nonatopic contro l subjects (C). AMs from AA showed a relatively high production of IL-1 beta and UL-6 (p<0. 05) and a relatively low secretion of IL-12 compared to C, whereas AMs from AN and C behaved similarly. This study confirmed previous findings that co -culture with AMs augments IL-5 production from allergen-stimulated CD4+ T- cells only in AA and not in nonasthmatics even if they are atopic. On the o ther hand, stimulation with allergen alone did not enhance IL-5 production by CD4+ T-cells in either AA nor AN. AM-induced changes in CD4+ T-cell IL-5 production upon allergen stimulation significantly correlated with their a bility to produce IL-1 beta (r=0.59, p<0.01), IL-6 (r=0.56, p<0.01), and in versely with IL-12 (r=-64, p=0.002) in all atopic subjects, and even more c losely with the ratio of IL-12/IL-1 beta (r=-0.75, p<0.001) and IL-12/IL-6 production (r=-0.81, p<0.001) in these subjects. These findings suggest that the role of alveolar macrophages from atopic as thmatics in enhancing interleukin-5 production by allergen-specific CD4+ T- cells is due, at least partly, to their aberrant production of interleukin- 1 beta, interleukin-6, and particularly of interleukin-12.