Proinflammatory cytokines can significantly induce human mononuclear phagocytes to produce nitric oxide by a cell maturation-dependent process

The capacity of three proinflammatory cytokines, interferon-gamma (rhifn-gamma), tumour-necrosis factor-alpha (rHTNF-(alpha) and interleukin-1 (rHIL-1), to induce release of nitric oxide (NO) from human mononuclear phagocytes were investigated. Peripheral blood monocytes were either used immediately or after culturing in vitro to develop into monocyte-derived macrophages (macrophages). Lipopolysaccharide (LPS) was used as second signal in all experiments. The three cytokines tested had significantly high enhancing influence on the production of nitric oxide by monocytes as well as by macrophages. However production was significantly higher by the monocytes matured in vitro to macrophages (P < 0.01). In our experimental system LPS had only marginal synergistic influence on production of NO2, and IFN-gamma demonstrated to be the most efficient of the three cytokines tested. Addition of L-arginine in the monocytes/macrophages culture further amplified production of NO2, whereas addition of N-G-monomethylarginine abrogated this amplification. We conclude that human mononuclear phagocytes are capable of using inducible nitric oxide synthase pathway to produce nitric oxide.