Nitric oxide blocks inflammatory cytokine secretion triggered by CD23 in monocytes from allergic, asthmatic patients and healthy controls

Abstract

In allergic asthma, monocytes/macrophages may be activated to produce inflammatory cytokines through triggering of the low-affinity IgE receptor (CD23). Elevated airway levels of nitric oxide (NO) are associated with asthmatic exacerbations. Our previous work suggested that NO may function in an anti-inflammatory capacity by downregulating endotoxin-stimulated cytokine production by alveolar macrophages and matured monocytes. The purpose of this study was to determine the effect of NO on CD23-triggered cytokine production by monocytes from asthmatic patients and healthy controls. Monocytes were obtained from normal volunteers (n = 13) and asthmatic patients with atopy (n = 8). Monocyte cultures were treated with interleukin-4 (IL-4) and granulocyte macrophage colony-stimulating factor (GM-CSF) for 24 hours to upregulate CD23 expression. Cultures were stimulated by anti-CD23 and treated with DETA NONOate [2,2-(hydroxynitrosohydrazonon)-bis-ethanamine] releases NO in culture with t(1/2) of 20 hours at 37 degrees C for 24 hours. Cell free culture supernatants were collected and assayed by enzyme-linked immunoadsorbent assay for macrophage inflammatory protein-1-alpha (MIP-1) and IL-6. NO inhibits MIP-1 secretion triggered by CD23 activation of IL-4- and GM-CSF-matured monocytes (percentage of MIP-1 suppression = 52 +/- 11 of monocytes from asthmatic patients; percentage = 55 +/- 8 healthy controls). The inhibitory effect of NO was not cytokine-specific, as similar results were obtained with IL-6 (50 +/- 9% IL-6 suppression, asthmatic patients; 66 +/- 20%, healthy controls). The results demonstrate for the first time an inhibitory effect of NO on cytokine production stimulated by CD23 receptor activation. We suggest that NO may be upregulated as a potent anti-inflammatory agent in the asthmatic lung.