title: Differential effects of fexofenadine on arachidonic acid metabolism in cultured human monocytes.
abstract: The relief of nasal congestion with the antihistamine fexofenadine in seasonal allergic rhinitis is thought to be due to its additional anti-inflammatory properties. The objective of this study was to evaluate the in vitro effects of fexofenadine on stimulated arachidonic acid metabolism. Human monocytes, isolated from blood and donated by 5 healthy volunteers, were either incubated for 20 h with 10 microg/ml lipopolysaccharide, with and without fexofenadine (10(-8)-10(-3) mol/l, n = 8-19), or were incubated for 20 h, with and without fexofenadine, and then stimulated with 0.5 mg/ml zymosan for 2 h. Leukotriene B4 (LTB4), LTC4, LTD4 and LTE4, prostaglandin E2 (PGE2) and F2alpha (PGF2alpha) production was determined by enzyme immunoassay. Zymosan-stimulated production of LTC4, LTD4 and LTE4 was significantly inhibited by clinically relevant concentrations of fexofenadine HCl: 10(-7) mol/l (22% inhibition vs. control, p = 0.008) and 10(-6) mol/l (24% inhibition vs. control, p = 0.020). Higher concentrations of fexofenadine (10(-4) and 10(-3) mol/l) inhibited LTB(4) generation. Lipopolysaccharide-stimulated production of PGE2 was significantly inhibited by fexofenadine HCl 10(-6) mol/l (26% inhibition, p = 0.035) and 10(-5) mol/l (40% inhibition, p = 0.001). Higher concentrations of fexofenadine HCl (10(-4) and 10(-3) mol/l) significantly inhibited PGF2alpha production by 50% (p = 0.026) and 63% (p = 0.001), respectively. Fexofenadine, at both clinically relevant and higher concentrations, inhibits LTC4, LTD4, LTE4 and PGE2 in cultured human monocytes. These additional anti-inflammatory properties may underlie the relief of nasal congestion observed in clinical studies.
authors.affiliation: Department of Pneumology, Allergology and Sleep Medicine Medical Outpatient Clinic, University of Bonn, Bonn, Germany. uwejuergens@t-online.de
authors.forename: Uwe R
authors.initials: UR
authors.lastname: Juergens
authors.forename: Wilfried
authors.initials: W
authors.lastname: Darlath
authors.forename: Meinolf
authors.initials: M
authors.lastname: Stober
authors.forename: Kurt
authors.initials: K
authors.lastname: Racké
authors.forename: Selcuk
authors.initials: S
authors.lastname: Tasci
authors.forename: Adrian
authors.initials: A
authors.lastname: Gillissen
authors.forename: Hans
authors.initials: H
authors.lastname: Vetter
mesh_terms: D018926:Anti-Allergic Agents / Q000494:pharmacology*; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D016718:Arachidonic Acid / Q000378:metabolism*; D002478:Cells, Cultured; D015232:Dinoprostone / Q000378:metabolism; D006634:Histamine H1 Antagonists / Q000494:pharmacology*; D006801:Humans; D015289:Leukotrienes / Q000378:metabolism; D008070:Lipopolysaccharides; D009000:Monocytes / Q000187:drug effects / Q000378:metabolism; D016593:Terfenadine / Q000031:analogs & derivatives* / Q000494:pharmacology; D015054:Zymosan
chemical_list: D018926:Anti-Allergic Agents; D000893:Anti-Inflammatory Agents; D006634:Histamine H1 Antagonists; D015289:Leukotrienes; D008070:Lipopolysaccharides; D016718:Arachidonic Acid; D016593:Terfenadine; D015054:Zymosan; C093230:fexofenadine; D015232:Dinoprostone