title: The anti-inflammatory potency of dexamethasone is determined by the route of application in vivo.
abstract: Glucocorticoids (GC) are highly potent anti-inflammatory agents frequently administered in clinical medicine. However, even for the most potent GC dexamethasone, only modest effects have been observed in several murine studies. Here we demonstrate that intraperitoneal administration of dexamethasone displays no anti-inflammatory activity in two different mouse models. Low doses of topically applied dexamethasone entirely prevented ear swelling in a contact hypersensitivity model in BALB/c mice, while intraperitoneally injected dexamethasone had no effect on disease progression. Moreover, subcutaneously administered dexamethasone completely inhibited lipopolysaccharide (LPS)-mediated lethality in C57BL/6 mice. In contrast, even ultra-high doses of intraperitoneally injected dexamethasone could not prevent endotoxin-induced death. In conclusion, these results demonstrate that intraperitoneal application of dexamethasone is ineffective in these models of inflammation, which has broad implications for mouse models evaluating the in vivo efficiency of GCs.
authors.forename: Thomas
authors.initials: T
authors.lastname: Weichhart
authors.forename: Oliver
authors.initials: O
authors.lastname: Brandt
authors.forename: Caroline
authors.initials: C
authors.lastname: Lassnig
authors.forename: Mathias
authors.initials: M
authors.lastname: Müller
authors.forename: Walter H
authors.initials: WH
authors.lastname: Hörl
authors.forename: Georg
authors.initials: G
authors.lastname: Stingl
authors.forename: Marcus D
authors.initials: MD
authors.lastname: Säemann
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage*; D003877:Dermatitis, Contact / Q000188:drug therapy* / Q000276:immunology / Q000503:physiopathology; D003907:Dexamethasone / Q000008:administration & dosage*; D004195:Disease Models, Animal; D018450:Disease Progression; D004333:Drug Administration Routes; D019446:Endotoxemia / Q000139:chemically induced / Q000188:drug therapy* / Q000276:immunology / Q000503:physiopathology; D007109:Immunity / Q000187:drug effects; D007249:Inflammation; D008070:Lipopolysaccharides / Q000008:administration & dosage; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D010081:Oxazolone / Q000008:administration & dosage
chemical_list: D000893:Anti-Inflammatory Agents; D008070:Lipopolysaccharides; D010081:Oxazolone; D003907:Dexamethasone