Inhibitory effect of loratadine on leukotriene B4 production by neutrophils either alone or during interaction with human airway epithelial cells

Abstract

Leukotriene B4 (LTB4), an inflammatory mediator, is a potent chemoattractant for neutrophils (PMN) that plays an important role in the late reaction in asthma. Human airway epithelial cells (HAEC) can interact with PMN to increase LTB4 production. The aim of this study was to determine the influence of loratadine, an antihistaminic drug, on the production of LTB4 by PMN either alone or during interaction with transformed HAEC. The effect of tumour necrosis factor-alpha (TNF-alpha) was also examined. LTB4 production was measured by RP-HPLC after cell stimulation with calcium ionophore. Loratadine (0.25-25 microM) induced a significant and dose-dependent decrease of LTB4 production by PMN alone whereas it was up-regulated by TNF-alpha. As reported by others, we confirmed the increase of LTB4 release when PMN were cocultured with HAEC as compared to PMN alone. Addition of loratadine to HAEC before co-culture with PMN induced a significant decrease of LTB4 formation by cell interaction. This effect was noted when HAEC were washed following incubation with loratadine, demonstrating a direct action of the drug on this cell type. Moreover, the TNF-alpha-induced stimulation of LTB4 release that we demonstrated in PMN-HAEC interaction was also inhibited by loratadine. These results indicate that loratadine might reduce inflammatory reaction by a direct effect on PMN LTB4 production but also through an influence on HAEC during interaction with PMN.