title: Cholera toxin B pretreatment of macrophages and monocytes diminishes their proinflammatory responsiveness to lipopolysaccharide.
abstract: The cholera toxin B chain (CTB) has been reported to suppress T cell-dependent autoimmune diseases and to potentiate tolerance of the adaptive immune system. We have analyzed the effects of CTB on macrophages in vitro and have found that preincubation with CTB (10 microg/ml) suppresses the proinflammatory reaction to LPS challenge, as demonstrated by suppressed production of TNF-alpha, IL-6, IL-12(p70), and NO (p < 0.01) in cells of macrophage lines. Pre-exposure to CTB also suppresses LPS-induced TNF-alpha and IL-12(p70) formation in human PBMC. Both native and recombinant CTB exhibited suppressive activity, which was shared by intact cholera toxin. In cells of the human monocyte line Mono Mac 6, exposure to CTB failed to suppress the production of IL-10 in response to LPS. Control experiments excluded a role of possible contamination of CTB by endotoxin or intact cholera toxin. The suppression of TNF-alpha production occurred at the level of mRNA formation. Tolerance induction by CTB was dose and time dependent. The suppression of TNF-alpha and IL-6 production could be counteracted by the addition of Abs to IL-10 and TGF-beta. IFN-gamma also antagonized the actions of CTB on macrophages. In contrast to desensitization by low doses of LPS, tolerance induction by CTB occurred silently, i.e., in the absence of a measurable proinflammatory response. These findings identify immune-deviating properties of CTB at the level of innate immune cells and may be relevant to the use of CTB in modulating immune-mediated diseases.
authors.affiliation: German Diabetes Research Institute, University of Dusseldorf, Dusseldorf, Germany.
authors.forename: Volker
authors.initials: V
authors.lastname: Burkart
authors.forename: Yoong-Eun
authors.initials: YE
authors.lastname: Kim
authors.forename: Bettina
authors.initials: B
authors.lastname: Hartmann
authors.forename: Iona
authors.initials: I
authors.lastname: Ghiea
authors.forename: Ulrike
authors.initials: U
authors.lastname: Syldath
authors.forename: Manfred
authors.initials: M
authors.lastname: Kauer
authors.forename: Waltraud
authors.initials: W
authors.lastname: Fingberg
authors.forename: Pejman
authors.initials: P
authors.lastname: Hanifi-Moghaddam
authors.forename: Sylvia
authors.initials: S
authors.lastname: Müller
authors.forename: Hubert
authors.initials: H
authors.lastname: Kolb
mesh_terms: D000818:Animals; D000906:Antibodies / Q000494:pharmacology; D002460:Cell Line; D002478:Cells, Cultured; D002772:Cholera Toxin / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D006801:Humans; D007371:Interferon-gamma / Q000494:pharmacology; D016753:Interleukin-10 / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000276:immunology; D018664:Interleukin-12 / Q000096:biosynthesis; D015850:Interleukin-6 / Q000096:biosynthesis; D007700:Kinetics; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000276:immunology; D008070:Lipopolysaccharides / Q000037:antagonists & inhibitors*; D008264:Macrophages / Q000187:drug effects / Q000276:immunology*; D051379:Mice; D009000:Monocytes / Q000187:drug effects / Q000276:immunology*; D009569:Nitric Oxide / Q000096:biosynthesis; D012333:RNA, Messenger / Q000096:biosynthesis; D016212:Transforming Growth Factor beta / Q000037:antagonists & inhibitors / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis / Q000235:genetics
chemical_list: D000906:Antibodies; D015850:Interleukin-6; D008070:Lipopolysaccharides; D012333:RNA, Messenger; D016212:Transforming Growth Factor beta; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D018664:Interleukin-12; D009569:Nitric Oxide; D007371:Interferon-gamma; D002772:Cholera Toxin