Nitric oxide inhibits inflammatory cytokine production by human alveolar macrophages.
High levels of nitric oxide (NO) have been reported in exhaled air of asthmatic individuals. Because alveolar macrophages (AM) are major producers of cytokines, and bronchoalveolar lavage fluid (BALF) from asthmatic individuals contains increased levels of inflammatory cytokines, this study was undertaken to determine whether NO modified the production of inflammatory cytokines by human AM. AM were obtained from normal volunteers by fiberoptic bronchoscopy. Tumor necrosis factor-alpha (TNF-alpha) production stimulated by lipopolysaccharide (LPS; 0.5 microg/ml) was measured with an enzyme-linked immunosorbent assay (ELISA). NO generated from 2,2-(hydroxynitrosohydrazono)-bis-ethanamine (DETA NONOate) (0.1 to 1.0 mM) inhibited TNF-alpha secretion in a dose-dependent manner. At 1 mM DETA NONOate, mean inhibition (+/- SEM) of TNF-alpha secretion was 56 +/- 4% (P = 0.002). To determine whether this effect was cytokine specific, interleukin-1beta (IL-1beta) and macrophage inflammatory protein-1alpha (MIP-1alpha) were evaluated, and DETA NONOate was also found to inhibit both of these cytokines. Basal cytokine levels from unstimulated AM were unaffected by NO. These findings indicate that NO is a potent inhibitor of cytokine production by stimulated human AM.
Thomassen
M J
MJ
Department of Pulmonary and Critical Care Medicine, The Cleveland Clinic Foundation, Ohio 44195-5038, USA. thomasm@cesmtp.ccf.org
Buhrow
L T
LT
Connors
M J
MJ
Kaneko
F T
FT
Erzurum
S C
SC
Kavuru
M S
MS
D002470:Cell Survival / Q000187:drug effects / Q000276:immunology; D054405:Chemokine CCL3; D054407:Chemokine CCL4; D016207:Cytokines / Q000096:biosynthesis* / Q000276:immunology; D006801:Humans; D008070:Lipopolysaccharides / Q000494:pharmacology; D019402:Macrophage Inflammatory Proteins / Q000037:antagonists & inhibitors; D016676:Macrophages, Alveolar / Q000166:cytology / Q000276:immunology* / Q000378:metabolism*; D009569:Nitric Oxide / Q000494:pharmacology*; D009603:Nitroso Compounds / Q000494:pharmacology
D054405:Chemokine CCL3; D054407:Chemokine CCL4; D016207:Cytokines; D008070:Lipopolysaccharides; D019402:Macrophage Inflammatory Proteins; D009603:Nitroso Compounds; C094210:2,2'-(hydroxynitrosohydrazono)bis-ethanamine; D009569:Nitric Oxide