In:
Pharmacology, S. Karger AG, Vol. 76, No. 1 ( 2006), p. 40-45
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 〈 sup 〉 –8 〈 /sup 〉 –10 〈 sup 〉 –3 〈 /sup 〉 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 B 〈 sub 〉 4 〈 /sub 〉 (LTB 〈 sub 〉 4 〈 /sub 〉 ), LTC 〈 sub 〉 4 〈 /sub 〉 , LTD 〈 sub 〉 4 〈 /sub 〉 and LTE 〈 sub 〉 4 〈 /sub 〉 , prostaglandin E 〈 sub 〉 2 〈 /sub 〉 (PGE 〈 sub 〉 2 〈 /sub 〉 ) and F 〈 sub 〉 2 〈 /sub 〉 α(PGF 〈 sub 〉 2 〈 /sub 〉 α) production was determined by enzyme immunoassay. Zymosan-stimulated production of LTC 〈 sub 〉 4 〈 /sub 〉 , LTD 〈 sub 〉 4 〈 /sub 〉 and LTE 〈 sub 〉 4 〈 /sub 〉 was significantly inhibited by clinically relevant concentrations of fexofenadine HCl: 10 〈 sup 〉 –7 〈 /sup 〉 mol/l (22% inhibition vs. control, p = 0.008) and 10 〈 sup 〉 –6 〈 /sup 〉 mol/l (24% inhibition vs. control, p = 0.020). Higher concentrations of fexofenadine (10 〈 sup 〉 –4 〈 /sup 〉 and 10 〈 sup 〉 –3 〈 /sup 〉 mol/l) inhibited LTB 〈 sub 〉 4 〈 /sub 〉 generation. Lipopolysaccharide-stimulated production of PGE 〈 sub 〉 2 〈 /sub 〉 was significantly inhibited by fexofenadine HCI 10 〈 sup 〉 –6 〈 /sup 〉 mol/l (26% inhibition, p = 0.035) and 10 〈 sup 〉 –5 〈 /sup 〉 mol/l (40% inhibition, p = 0.001). Higher concentrations of fexofenadine HCI (10 〈 sup 〉 –4 〈 /sup 〉 and 10 〈 sup 〉 –3 〈 /sup 〉 mol/l) significantly inhibited PGF 〈 sub 〉 2 〈 /sub 〉 α production by 50% (p = 0.026) and 63% (p = 0.001), respectively. Fexofenadine, at both clinically relevant and higher concentrations, inhibits LTC 〈 sub 〉 4 〈 /sub 〉 , LTD 〈 sub 〉 4 〈 /sub 〉 , LTE 〈 sub 〉 4 〈 /sub 〉 and PGE 〈 sub 〉 2 〈 /sub 〉 in cultured human monocytes. These additional anti-inflammatory properties may underlie the relief of nasal congestion observed in clinical studies.
Type of Medium:
Online Resource
ISSN:
0031-7012
,
1423-0313
Language:
English
Publisher:
S. Karger AG
Publication Date:
2006
detail.hit.zdb_id:
1483550-2
SSG:
15,3
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