title: Effects of prednisolone on the systemic release of mediators of cell-mediated cytotoxicity during human endotoxemia.
abstract: Corticosteroids are widely used for the suppression of cell-mediated cytoxicity. This process is mediated by natural killer cells and cytotoxic T lymphocytes, and their activation can be monitored by levels of the chemokines CXCL9 and CXCL10, the degranulation product granzymes A and B, and by levels of secretory phospholipase A2. The current study aimed to determine the effects of increasing doses of prednisolone on the release of these mediators in healthy humans exposed to LPS. Therefore, 32 healthy men received prednisolone orally at doses of 0, 3, 10, or 30 mg (n = 8 per group) at 2 h before intravenous injection of Escherichia coil LPS (4 ng/kg). Prednisolone dose-dependently attenuated the LPS-induced rises in the plasma concentrations of the chemokines CXCL9 and CXCL10, as well as of granzymes A and B levels. CXCL10 and granzyme B release were most sensitive to prednisolone, with a significant inhibition already achieved at the lowest prednisolone dose (3 mg). The levels of secretory phospholipase A2 were increased after LPS administration but were not significantly affected by prednisolone. This study demonstrates that prednisolone differentially inhibits the systemic release of mediators involved in cell-mediated cytotoxicity in humans in vivo.
authors.affiliation: Center for Experimental and Molecular Medicine, Academic Medical Center, University of Amsterdam, The Netherlands. m.d.dekruif@amc.uva.nl
authors.forename: Martijn D
authors.initials: MD
authors.lastname: de Kruif
authors.forename: Luclenne C
authors.initials: LC
authors.lastname: Lemaire
authors.forename: Ida A
authors.initials: IA
authors.lastname: Giebelen
authors.forename: Angelique P
authors.initials: AP
authors.lastname: Groot
authors.forename: Jennie M
authors.initials: JM
authors.lastname: Pater
authors.forename: Petra S
authors.initials: PS
authors.lastname: van den Pangaart
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Elliott
authors.forename: Tom
authors.initials: T
authors.lastname: van der Poll
mesh_terms: D000284:Administration, Oral; D000328:Adult; D054357:Chemokine CXCL10 / Q000097:blood; D054370:Chemokine CXCL9 / Q000097:blood; D003602:Cytotoxicity, Immunologic / Q000187:drug effects* / Q000276:immunology; D004305:Dose-Response Relationship, Drug; D019446:Endotoxemia / Q000097:blood / Q000276:immunology*; D053804:Granzymes / Q000097:blood; D006801:Humans; D007275:Injections, Intravenous; D007694:Killer Cells, Natural / Q000166:cytology / Q000276:immunology; D008070:Lipopolysaccharides / Q000008:administration & dosage / Q000494:pharmacology; D008297:Male; D011239:Prednisolone / Q000008:administration & dosage / Q000494:pharmacology*; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology*; D013602:T-Lymphocytes, Cytotoxic / Q000166:cytology / Q000276:immunology
chemical_list: D054357:Chemokine CXCL10; D054370:Chemokine CXCL9; D008070:Lipopolysaccharides; D011239:Prednisolone; D053804:Granzymes