Inhibition of mediator and cytokine release from dispersed nasal polyp cells by terfenadine

The mechanism of action of H-1-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 mu mol) on the release of leukotrienes (LT) (LTC(4)/D-4 and LTB(4)) 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 LTC(4)/D-4, LTB(4), TNF-alpha, and GM-CSF. IC50 values were determined for LTC(4)/D-4 (8 mu mol), LTB(4) (9.9 mu mol), TNF-alpha (6.1 mu mol), and GM-CSF (4 mu mol). 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.