Chloroquine inhibits inducible nitric oxide synthase expression in murine peritoneal macrophages

Induction of inducible nitric oxide synthase in vivo or in vitro in respons e to stimuli is only temporary However, chronic localized expression of ind ucible nitric oxide synthase in certain organs has been associated with the development of autoimmune diseases or chronic inflammatory diseases. Chlor oquine is being used as an antiinflammatory drug, and its inhibitory effect on the synthesis of pro-inflammatory cytokines, such as tumour necrosis fa ctor-cc and interferon-gamma, has been reported. In this study, we examined whether chloroquine could inhibit nitric oxide synthesis in murine periton eal macrophages stimulated with interferon-gamma and lipopolysaccharide. Al though prolonged incubation of cells with high concentrations of chloroquin e showed some cytotoxicity, the drug itself was not cytotoxic when macropha ges were preincubated with chloroquine for 2 hr, washed and stimulated with interferon-gamma and lipopolysaccharide in the absence of chloroquine for another 48 hr. The nitric oxide production from stimulated macrophages was markedly reduced by chloroquine in a dose-dependent manner and induction of inducible nitric oxide synthase mRNA was also suppressed by chloroquine pr etreatment. These results show that chloroquine inhibits the induction of i nducible nitric oxide synthase from interferon-gamma and lipopolysaccharide -stimulated macrophages, thereby reducing nitric oxide synthesis.