Morphine inbibits NF-kappa B nuclear binding in human neutrophils and monocytes by a nitric oxide-dependent mechanism

Background The transcription factor NF-kappa B plays a pivotal role in gene expression of inflammatory mediators such as cytokines or adhesion molecul es. NF-kappa B-mediated transcriptional activation of these genes is inhibi ted by nitric oxide (NO) in a variety of cells, including monocytes. Morphi ne mediates NO release in a naloxone antagonizable manner in monocytes and neutrophils. Methods: The influence of morphine on NF-kappa B activation was investigate d ill a whole-blood flow cytometric assay. A specific antibody against the p65 subunit of NF-kappa B was used and detected by fluroresceine-isothiocya nate-labeled anti-immunoglobulin G. Nuclei mere stained with propidium iodi de. Leukocyte subpopulations were evaluated by gating on neutrophils and mo nocytes. The median fluorescence channel was determined. Different morphine concentrations (50 nm, 50 mu M, 1 mM) and incubation intervals (10-150 min ) were used. Results: Morphine inhibits lipopolysaccharide-induced NF-kappa B nuclear bi nding in human blood neutrophils and monocytes in a time-, concentration-, and naloxone-sensitive-dependent manner. Similar effects mere achieved with the NO donor S-nitroso-N-acetyl-pencillamine and the antioxidant N-acetyl- cysteine. The NO synthase inhibitors N-omega-nitro-L-arginine-methyl-esther and N-omega-nitro-L-arginine completely abolished the morphine-induced att enuation of NF-kappa B nuclear binding, demonstrating that the inhibitory a ction is mediated by NO release. Conclusion Morphine causes immunosuppression, at least in part, via the NO- stimulated depression of NF-kappa B nuclear binding.