Differential effects of fexofenadine on arachidonic acid metabolism in cultured human monocytes.
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.
Juergens
Uwe R
UR
Department of Pneumology, Allergology and Sleep Medicine Medical Outpatient Clinic, University of Bonn, Bonn, Germany. uwejuergens@t-online.de
Darlath
Wilfried
W
Stober
Meinolf
M
Racké
Kurt
K
Tasci
Selcuk
S
Gillissen
Adrian
A
Vetter
Hans
H
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
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