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Suplatast tosilate inhibits thymus- and activation-regulated chemokine production by antigen-specific human Th2 cells


Kenji Minoguchi, MD, PhD, First Department of Internal Medicine, Showa University, School of Medicine, 1-5-8 Hatanodai, Shinagawa-ku, Tokyo 142, Japan. E-mail:


Background Suplatast tosilate is an anti-allergic agent that suppresses cytokine production by human Th2 cells.

Objective We investigated the effects of suplatast tosilate on the production of thymus- and activation-regulated chemokine (TARC) by T cells from allergic patients with asthma.

Methods Purified protein derivative (PPD)-specific Th1 cell lines and Dermatophagoides farinae (Der f)-specific Th2 cell lines were established from nine patients with house dust mite-allergic asthma. The effects of suplatast tosilate on mRNA expression of TARC and protein production of TARC from antigen-specific Th1 or Th2 cell lines were investigated after stimulation with relevant antigens or phytohemagglutinin (PHA). In addition, the effects of IL-4, IL-10, and IFN-γ on TARC production by Der f-specific Th2 cell lines in the presence or absence of suplatast tosilate were studied.

Results Although PPD-specific Th1 cell lines did not produce TARC after stimulation with PPD antigen or PHA, stimulation of Der f-specific Th2 cell lines with Der f antigen or PHA increased production of TARC. Suplatast tosilate significantly and dose-dependently inhibited production of TARC by Der f-specific Th2 cell lines stimulated with either Der f antigen (76.5% inhibition at 100 µg/mL, P < 0.01) or PHA (81.9% inhibition at 100 µg/mL, P < 0.01). TARC production by Der f-specific Th2 cell lines was significantly increased only by activation with IL-4 but not with IL-10 or IFN-γ; this increase in TARC production was significantly inhibited by suplatast tosilate (97.5% inhibition at 100 µg/mL, P < 0.01).

Conclusion Suplatast tosilate inhibits TARC production by human Th2 cells. Therefore, this agent inhibits both Th2 cytokine and Th2 chemokine and may be a useful anti-allergic agent.