title: Reduction of lipopolysaccharide-induced interleukin-6 production by the kappa opioid U50,488 in a mouse monocyte-like cell line.
abstract: Several studies demonstrate that opioids modulate the immune response via opioid receptors expressed directly on the immune cells themselves. Recently, it has been suggested that the kappa opioid system has a modulatory role in various inflammatory diseases including rheumatoid arthritis. This modulation may occur via changes in cytokine secretion by monocyte-derived cells. To further study this opioid-immune relationship, we stimulated P388D1 cells, a mouse monocyte-like cell line, with lipopolysaccharide (LPS) in the presence or absence of the kappa opioid-selective ligand, U50,488. Pretreatment with U50,488 significantly reduced LPS-stimulated interleukin-6 (IL-6) production as measured by ELISA. This effect was mediated by the kappa opioid receptor, because nor-binaltorphimine (nor-BNI), a kappa-selective antagonist, blocked this inhibition. It is likely that this reduction of IL-6 protein by U50,488 treatment is attributed to decreases in IL-6 mRNA. RT-PCR experiments demonstrated that U50,488 treatment significantly reduced the LPS-mediated increase in IL-6 mRNA and that this effect was also blocked by nor-BNI. Understanding the mechanism behind the reduction of proinflammatory cytokine production by opioids may lead to the development of more effective therapeutics for inflammatory diseases.
authors.affiliation: Department of Pharmacology and Physiology, P.O. Box 711, University of Rochester, School of Medicine and Dentistry, 601 Elmwood Avenue, Rochester, NY 14642-8711, USA.
authors.forename: Amy L
authors.initials: AL
authors.lastname: Parkhill
authors.forename: Jean M
authors.initials: JM
authors.lastname: Bidlack
mesh_terms: D019900:3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer / Q000494:pharmacology*; D000818:Animals; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D003609:Dactinomycin / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)- / Q000494:pharmacology; D020881:Enkephalin, D-Penicillamine (2,5)- / Q000494:pharmacology; D015870:Gene Expression / Q000187:drug effects; D015850:Interleukin-6 / Q000235:genetics / Q000378:metabolism*; D008070:Lipopolysaccharides / Q000494:pharmacology*; D051379:Mice; D009000:Monocytes / Q000187:drug effects* / Q000378:metabolism; D009271:Naltrexone / Q000031:analogs & derivatives / Q000494:pharmacology; D009292:Narcotic Antagonists / Q000494:pharmacology; D009842:Oligopeptides / Q000494:pharmacology; D020871:RNA Stability / Q000187:drug effects; D017473:Receptors, Opioid, kappa / Q000819:agonists; D013997:Time Factors; D014158:Transcription, Genetic / Q000187:drug effects; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D015850:Interleukin-6; D008070:Lipopolysaccharides; D009292:Narcotic Antagonists; D009842:Oligopeptides; D017473:Receptors, Opioid, kappa; D014409:Tumor Necrosis Factor-alpha; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; C060209:deltorphin II, Ala(2)-; D003609:Dactinomycin; C051844:norbinaltorphimine; D009271:Naltrexone; D019900:3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer; D020881:Enkephalin, D-Penicillamine (2,5)-