Differential Effects of Fexofenadine on Arachidonic Acid Metabolism in Cultured Human Monocytes

Vol. 76, No. 1, 2006

Free Abstract Article (References) Article (PDF 172 KB)

Original Paper

Differential Effects of Fexofenadine on Arachidonic Acid Metabolism in Cultured Human Monocytes
Uwe R. Juergens^a, Wilfried Darlath^d, Meinolf Stöber^a, Kurt Racké^c, Selcuk Tasci^b, Adrian Gillissen^e, Hans Vetter^a

^aDepartment of Pneumology, Allergology and Sleep Medicine Medical Outpatient Clinic, and
^bDepartment of Internal Medicine 2, University Hospital Bonn,
^cDepartment of Pharmacology and Toxicology, University of Bonn, Bonn,
^dClinical Development, Aventis Pharma Germany, Bad Soden, and
^eSt. George Medical Center, Robert-Koch Hospital, Leipzig, Germany

Address of Corresponding Author

Pharmacology 2006;76:40-45 (DOI: 10.1159/000089263)

Key Words

Allergic rhinitis
Antihistamine
Arachidonic acid
Fexofenadine

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 µg/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 F₂ alpha (PGF₂ alpha ) 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^-7mol/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 LTB₄ generation. Lipopolysaccharide-stimulated production of PGE₂ was significantly inhibited by fexofenadine HCI 10^-6 mol/l (26% inhibition, p = 0.035) and 10^-5 mol/l (40% inhibition, p = 0.001). Higher concentrations of fexofenadine HCI (10^-4 and 10^-3 mol/l) significantly inhibited PGF₂ alpha 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.

Author Contacts

Prof. Dr. Uwe R. Juergens
Department of Pneumology, Allergology and Sleep Medicine
Medical Outpatient Clinic, Bonn University Hospital
Wilhelmstrasse 35-37, DE-53111 Bonn (Germany)
Tel. +49 228 287 2251, Fax +49 228 287 2266, E-Mail uwejuergens@t-online.de

Article Information

Received: July 28, 2005
Accepted: August 10, 2005
Published online: October 26, 2005
Number of Print Pages : 6
Number of Figures : 3, Number of Tables : 2, Number of References : 23

Medline Abstract (ID 16254456)

Download Citation

This journal is part of the second subject package of the Karger

Journal Archive Collection

Information on packages (PDF)
Free sample issues

For non-native English speakers and international authors who would like assistance with their writing before submission, we suggest American Journal Experts for their scientific editing service.