title: Glucocorticoid-induced modulation of cytokine secretion from normal and leukemic human myelomonocytic cells.
abstract: Since glucocorticoid effects on inflammatory processes may be mediated via modulation of cytokine release, different types of myelomonocytic cells were stimulated in vitro with lipopolysaccharide (50 ng/ml) or phorbol myristate acetate (25 ng/ml) plus the ionophore A23187, 2 x 10(-7) M, and release of interleukin (IL)-1 beta, IL-8 and tumor necrosis factor (TNF)-alpha was measured after 24 h by ELISA. Peripheral blood mononuclear cells from two allergic and two normal human donors released similarly large quantities of IL-8 and lower amounts of IL-1 beta and TNF-alpha. This also held for myelomonocytic cell lines, with THP-1 cells being most active, followed by U-937 and HL-60 cells. All potent glucocorticoids studied caused a dose-dependent inhibition of cytokine release from donor cells, being most marked for IL-1 beta and lowest for IL-8. Inhibition of cytokine release was also noted with U-937 cells, with clear differences in potency between the glucocorticoids, whereas release was enhanced in all experiments with THP-1 cells. These results were confirmed with Northern blot analysis. Modulating effects of glucocorticoids on cytokine release are thus complex, and are particularly dependent on the cell type studied.
authors.affiliation: Department of Dermatology, Virchow Clinics of Humboldt University, Berlin, Germany.
authors.forename: P
authors.initials: P
authors.lastname: Welker
authors.forename: U
authors.initials: U
authors.lastname: Lippert
authors.forename: W
authors.initials: W
authors.lastname: Nürnberg
authors.forename: S
authors.initials: S
authors.lastname: Krüger-Krasagakes
authors.forename: A
authors.initials: A
authors.lastname: Möller
authors.forename: B M
authors.initials: BM
authors.lastname: Czarnetzki
mesh_terms: D000287:Administration, Topical; D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D016207:Cytokines / Q000097:blood / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D005938:Glucocorticoids / Q000494:pharmacology*; D006801:Humans; D015479:Leukemia, Myelomonocytic, Acute / Q000378:metabolism* / Q000473:pathology*; D015477:Leukemia, Myelomonocytic, Chronic / Q000378:metabolism* / Q000473:pathology*; D007963:Leukocytes, Mononuclear / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology; D008775:Methylprednisolone / Q000031:analogs & derivatives / Q000494:pharmacology; D014407:Tumor Cells, Cultured / Q000187:drug effects
chemical_list: D000893:Anti-Inflammatory Agents; D016207:Cytokines; D005938:Glucocorticoids; D008070:Lipopolysaccharides; C078007:methylprednisolone aceponate; D008775:Methylprednisolone