Journal article

Publication year: 2000

Pages: 1677-1684

Journal: Anesthesiology

Volume number: 92

Issue number: 6

ISSN: 0003-3022

eISSN: 1528-1175

Open access status: Bronze

DOI Link: https://doi.org/10.1097/00000542-200006000-00027

Publisher: Lippincott, Williams & Wilkins

Abstract: 

Background The transcription factor NF-kappa B plays a pivotal role in gene expression of inflammatory mediators such as cytokines or adhesion molecules. NF-kappa B-mediated transcriptional activation of these genes is inhibited by nitric oxide (NO) in a variety of cells, including monocytes. Morphine mediates NO release in a naloxone antagonizable manner in monocytes and neutrophils.

Methods: The influence of morphine on NF-kappa B activation was investigated ill a whole-blood flow cytometric assay. A specific antibody against the p65 subunit of NF-kappa B was used and detected by fluroresceine-isothiocyanate-labeled anti-immunoglobulin G. Nuclei mere stained with propidium iodide. Leukocyte subpopulations were evaluated by gating on neutrophils and monocytes. 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 binding 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 attenuation of NF-kappa B nuclear binding, demonstrating that the inhibitory action is mediated by NO release.

Conclusion Morphine causes immunosuppression, at least in part, via the NO-stimulated depression of NF-kappa B nuclear binding.

Harvard Citation style: Welters, I., Menzebach, A., Goumon, Y., Cadet, P., Menges, T., Hughes, T., et al. (2000) Morphine inbibits NF-κB nuclear binding in human neutrophils and monocytes by a nitric oxide-dependent mechanism, Anesthesiology, 92(6), pp. 1677-1684. https://doi.org/10.1097/00000542-200006000-00027

APA Citation style: Welters, I., Menzebach, A., Goumon, Y., Cadet, P., Menges, T., Hughes, T., Hempelmann, G., & Stefano, G. (2000). Morphine inbibits NF-κB nuclear binding in human neutrophils and monocytes by a nitric oxide-dependent mechanism. Anesthesiology. 92(6), 1677-1684. https://doi.org/10.1097/00000542-200006000-00027