Modulation of eicosanoid and histamine release from human dispersed lung cells by terfenadine.

Abstract

Terfenadine is an H1-blocker that may have antiallergic properties. A study was carried out to examine the ability of terfenadine to inhibit the release of histamine and arachidonic-acid-derived mediators from human lung cells. Cells were dispersed from fresh human lung tissue obtained from four accident victims whose hearts were donated for transplantation and four lung cancer resections. Cells were dispersed by enzymatic digestion with type XIV protease and chymopapain, and this resulted in a cell population containing approximately 5% mast cells. The remaining cells were mainly macrophages. The cells were challenged with anti-IgE at a 1/1000 dilution. Cells were challenged without terfenadine and after a preincubation of 0.1, 1, and 10 mumol terfenadine. The release of PGD2 and LTC4/D4 was assessed with an EIA. Histamine was assayed by RIA with a monoclonal antibody against acylated histamine. A release of both eicosanoids and histamine was observed in all experiments. An inhibition of eicosanoids was observed at both 1 and 10 mumol terfenadine (median percentage of inhibition of PGD2: 38.00 +/- 15.65 and 56.00 +/- 13.12; median percentage of inhibition of LTC4/D4: 37.5 +/- 19.80 and 52.5 +/- 26.8). On the other hand, histamine release was not blocked by terfenadine. Terfenadine inhibits, in a dose-dependent manner, the release of eicosanoids after challenge of dispersed lung cells by anti-IgE, and this effect may have some clinical relevance.