The Effect of Suplatast Tosilate on TARC Production in Peripheral Blood Mononuclear Cells and TARC Plasma Levels

Abstract

Background: Thymus and activation-regulated chemokine (TARC/CCL17) is a highly specific ligand for CCR 4. TARC may contribute to the recruitment, activation, and development of Th2 polarized cells that express CCR4. These characteristics have led investigators to hypothesize that TARC is involved in the development of Th2 responses. Suplatast tosilate ((±)-[2-[4-(3-ethoxy-2-hydroxy-propoxy) phenylcarbamoyl] ethyl] dimethylsulfonium p-toluenesulfonate) is an anti-allergic agent that selectively suppresses the synthesis of Th2 cytokines. We examined the effect of suplatast tosilate on TARC production and CCR-4 expression in vitro. Furthermore, we attempted to clarify whether TARC production was suppressed after clinical administration of suplatast tosilate. Methods: Peripheral blood mononuclear cells (PBMCs) were isolated from patients with allergic rhinitis who tested positive to house dust. PBMCs were stimulated with mite antigen. TARC mRNA was detected by real time PCR. The amount of TARC was estimated using an ELISA kit. PBMCs expressing CCR-4 were sorted by flow cytometry. The plasma level of TARC was examined in patients with chronic allergic rhinitis before and after treatment with suplatast tosilate for 4 weeks. Results: Suplatast tosilate significantly reduced TARC production by PBMCs. TARC mRNA was also suppressed in a concentration dependent manner. However, suplatast tosilate did not inhibit the expression of CCR-4 on PBMCs. The plasma level of TARC was significantly decreased in patients administered suplatast tosilate. Conclusions: Suplatast tosilate suppressed TARC production by PBMCs and decreased the plasma level of TARC in patients with chronic allergic rhinitis.

Keywords

• allergic rhinitis
• chemokines
• suplatast tosilate
• TARC