Suppressive Activity of Fexofenadine Hydrochloride on Thymus- and Activation-Regulated Chemokine Production from Human Peripheral Blood Leukocytes in Response to Antigenic Stimulation in vitro

Abstract

Background: Thymus- and activation-regulated chemokine (TARC) is accepted as being an important molecule in the development and maintenance of allergic diseases. However, there is little information about the influence of antiallergic agents on TARC production after allergen challenge. The aim of this study is to examine the influence of fexofenadine hydrochloride (FEX), an H₁-receptor antagonist, on TARC production from human peripheral blood leukocytes (PBL) using an in vitro cell culture technique. Methods: PBL prepared from donors with pollinosis were cultured with either Japanese cedar pollen allergen, Cry j 1, or interleukin (IL)-4 in the presence of various doses of FEX for 6 days. Levels of TARC and the T cell cytokines IL-4 and interferon (IFN)-γ in culture supernatants were examined by ELISA. Results: FEX did not affect PBL proliferation induced by Cry j 1 stimulation, even when 500 ng/ml of the agent, twice the therapeutic blood levels, was added to cell cultures as assessed by measuring ³H-thymidine incorporation into DNA. On the other hand, FEX at 250 ng/ml (but not 125 ng/ml), similar to therapeutic blood levels, significantly inhibited the ability of PBL to produce IL-4 (but not IFN-γ), which was enhanced by Cry j 1 stimulation. FEX at concentrations of more than 250 ng/ml also exerted a suppressive effect on TARC production from PBL in response to Cry j 1 and IL-4 stimulation in vitro. Conclusion: This inhibitory action of FEX may be partially responsible for the attenuating effect of the agent on allergic diseases.