Inhibition of mediator and cytokine release from dispersed nasal polyp cells by terfenadine.
The mechanism of action of H1-blockers requires elucidation because they may possess properties unrelated to the blockage of histamine at its receptor level. A study was performed with enzymatically dispersed cells obtained from nasal polyps to examine the effect of terfenadine (0.1-10 mumol) on the release of leukotrienes (LT) (LTC4/D4 and LTB4) after stimulation by anti-IgE, and on the spontaneous release of cytokines (granulocyte/macrophage-colony stimulating factor [GM-CSF] and tumor necrosis factor-alpha [TNF-alpha]) released from cells cultured for 6 h. Terfenadine inhibited significantly, and in a dose-dependent manner, the release of LTC4/D4, LTB4, TNF-alpha, and GM-CSF. IC50 values were determined for LTC4/D4 (8 mumol), LTB4 (9.9 mumol), TNF-alpha (6.1 mumol), and GM-CSF (4 mumol). Terfenadine was found to possess new antiallergic properties with a novel in vitro model which mimics more closely inflammatory cells of allergic rhinitis or asthma.
Crampette
L
L
Clinique des Maladies Respiratoires, Hôpital Arnaud de Villeneuve, Centre Hospitalier Universitaire, Montpellier, France.
Mainprice
B
B
Bloom
M
M
Bousquet
J
J
Campbell
A M
AM
D000293:Adolescent; D000328:Adult; D002478:Cells, Cultured; D016207:Cytokines / Q000037:antagonists & inhibitors* / Q000187:drug effects* / Q000378:metabolism; D005260:Female; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000037:antagonists & inhibitors / Q000187:drug effects / Q000378:metabolism; D006634:Histamine H1 Antagonists / Q000494:pharmacology*; D006801:Humans; D018836:Inflammation Mediators / Q000037:antagonists & inhibitors*; D020024:Leukotriene Antagonists; D007975:Leukotriene B4 / Q000037:antagonists & inhibitors / Q000378:metabolism; D017997:Leukotriene C4 / Q000037:antagonists & inhibitors / Q000378:metabolism; D015289:Leukotrienes / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009298:Nasal Polyps / Q000378:metabolism*; D016593:Terfenadine / Q000494:pharmacology*; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors / Q000187:drug effects / Q000378:metabolism
D016207:Cytokines; D006634:Histamine H1 Antagonists; D018836:Inflammation Mediators; D020024:Leukotriene Antagonists; D015289:Leukotrienes; D014409:Tumor Necrosis Factor-alpha; D007975:Leukotriene B4; D017997:Leukotriene C4; D016593:Terfenadine; D016178:Granulocyte-Macrophage Colony-Stimulating Factor