TUMOR-NECROSIS-FACTOR-ALPHA AND INTERLEUKIN-6 PRODUCTION BY HUMAN MONONUCLEAR PHAGOCYTES FROM ALLERGIC ASTHMATICS AFTER IGE-DEPENDENT STIMULATION

We have previously demonstrated the production of tumor necrosis factor-alpha (TNF) and interleukin-6 (IL-6) by alveolar macrophages (AM) from allergic asthmatics developing a late asthmatic reaction after bronchial allergen challenge. In order to explain the modalities of this monokine synthesis, we tested in vitro the effect of an IgE-dependent stimulation on blood monocytes (BM) and AM from control and asthmatic subjects. TNF and IL-6 secretions were evaluated in 24-h supernatants by radioimmunoassay and by the 7TD1 cell proliferation test, respectively. AM from allergic asthmatics secreted spontaneously higher concentrations of TNF and IL-6 then did BM or AM from control subjects. BM from asthmatics also produced spontaneously increased levels of TNF, but at a lesser degree than did AM. The addition of anti-IgE induced a significant increase of TNF and IL-6 secretions by mononuclear phagocytes from control subjects only after previous sensitization with IgE-rich medium. In contrast, the direct stimulation by allergen or anti-IgE of AM and BM from asthmatics enhanced significantly the production of TNF and IL-6 when compared with cells cultured in medium alone. In these conditions, IgE-dependent activation of cells from allergic asthmatics compared with those from control subjects increased monokine production in a similar manner. Costimulation by recombinant human interferon-gamma and IgE-dependent triggering had a synergistic effect on TNF production, but it had only an additive action on IL-6 synthesis (respective increase index: 9.8 compared with 2.9 and 9.8 compared with 2.1, respectively, for BM from control and asthmatic subjects). In order to avoid the influence of a potential contamination by low endotoxin concentration in the pneumoallergens and the antibody used in this study, we evaluated in the BM from patients presenting with drug hypersensitivity (amoxicillin, rifamycin, or myorelaxants) the production of cytokines after addition of pharmaceutically pure molecules. Drug addition to BM of such patients induced a low but significant increase of the secretion of TNF and IL,6 concentrations (p < 0.05 in both cases). In conclusion, we demonstrated that IgE-dependent activation enhances the TNF and IL-6 production by AM and BM. Moreover, the AM from asthmatics had an enhanced capacity to produce TNF and IL-6.