PMID- 9308913 OWN - NLM STAT- MEDLINE DCOM- 19971017 LR - 20131121 IS - 1044-1549 (Print) IS - 1044-1549 (Linking) VI - 17 IP - 3 DP - 1997 Sep TI - Nitric oxide inhibits inflammatory cytokine production by human alveolar macrophages. PG - 279-83 AB - 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. FAU - Thomassen, M J AU - Thomassen MJ AD - Department of Pulmonary and Critical Care Medicine, The Cleveland Clinic Foundation, Ohio 44195-5038, USA. thomasm@cesmtp.ccf.org FAU - Buhrow, L T AU - Buhrow LT FAU - Connors, M J AU - Connors MJ FAU - Kaneko, F T AU - Kaneko FT FAU - Erzurum, S C AU - Erzurum SC FAU - Kavuru, M S AU - Kavuru MS LA - eng PT - Journal Article PL - United States TA - Am J Respir Cell Mol Biol JT - American journal of respiratory cell and molecular biology JID - 8917225 RN - 0 (Chemokine CCL3) RN - 0 (Chemokine CCL4) RN - 0 (Cytokines) RN - 0 (Lipopolysaccharides) RN - 0 (Macrophage Inflammatory Proteins) RN - 0 (Nitroso Compounds) RN - 146724-94-9 (2,2'-(hydroxynitrosohydrazono)bis-ethanamine) RN - 31C4KY9ESH (Nitric Oxide) SB - IM MH - Cell Survival/drug effects/immunology MH - Chemokine CCL3 MH - Chemokine CCL4 MH - Cytokines/*biosynthesis/immunology MH - Humans MH - Lipopolysaccharides/pharmacology MH - Macrophage Inflammatory Proteins/antagonists & inhibitors MH - Macrophages, Alveolar/cytology/*immunology/*metabolism MH - Nitric Oxide/*pharmacology MH - Nitroso Compounds/pharmacology EDAT- 1997/10/06 00:00 MHDA- 1997/10/06 00:01 CRDT- 1997/10/06 00:00 PHST- 1997/10/06 00:00 [pubmed] PHST- 1997/10/06 00:01 [medline] PHST- 1997/10/06 00:00 [entrez] AID - 10.1165/ajrcmb.17.3.2998m [doi] PST - ppublish SO - Am J Respir Cell Mol Biol. 1997 Sep;17(3):279-83. doi: 10.1165/ajrcmb.17.3.2998m.