Differential regulation of human blood monocyte and alveolar macrophage inflammatory cytokine production by nitric oxide

Background: Nitric oxide (NO) has been associated with airway inflammation in asthma. Our previous work suggests that NO functions in an anti-inflamma tory capacity through downregulation of stimulated cytokine secretion by no rmal human alveolar macrophages. Functional differences between alveolar ma crophages and blood monocytes are thought to be related to maturation. Objective: The purpose of this study was to determine the effect of NO on s timulated cytokine production by monocytes from asthmatics and normal healt hy controls. Methods: Monocytes and alveolar macrophages were obtained from normal volun teers (n = 13) and asthmatics with atopy (n = 7). Monocyte and alveolar mac rophage cultures were stimulated with 0.5 mu g/mL lipopolysaccharide +/- 1. 0 mM DETA NONOate (releases NO in culture with t(1/2) = 20 hours at 37 degr ees C) and incubated for 24 hours. Cell-free supernatants were collected an d assayed by ELISA for tumor necrosis factor-alpha (TNF) and granulocyte ma crophage colony stimulating factor (GM-CSF). Results: Nitric oxide did not inhibit TNF production in monocytes of asthma tics and normals (mean +/- SEM % TNF stimulation = 19.6 +/- 9.7). Similar t o previous results, NO did inhibit alveolar macrophages (% TNF suppression = 60.6 +/- 4.4). To determine whether this differential effect of NO on the two cell populations was related to maturation, monocytes were matured by culture for 7 days. The in vitro matured monocytes demonstrated 51.7 +/- 7. 9% suppression of TNF. For each cell population, the responses of the asthm atics and healthy controls were not different. The differential effect is n ot cytokine specific Since similar results were obtained with GM-CSF. Conclusion: These results demonstrate a differential effect of NO on monocy te and alveolar macrophages cytokine regulation and this effect may be rela ted to the state of maturation.