Suplatast tosilate inhibits thymus- and activation-regulated chemokine production by antigen-specific human Th2 cells.
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-gamma 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 microg/mL, P < 0.01) or PHA (81.9% inhibition at 100 microg/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-gamma; this increase in TARC production was significantly inhibited by suplatast tosilate (97.5% inhibition at 100 microg/mL, P < 0.01).


CONCLUSIONS
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.
Oda
N
N
First Department of Internal Medicine, Showa University, Tokyo, Japan.
Minoguchi
K
K
Tanaka
A
A
Yokoe
T
T
Minoguchi
H
H
Matsuo
H
H
Nakashima
M
M
Tasaki
T
T
Adachi
M
M
D000328:Adult; D018926:Anti-Allergic Agents / Q000494:pharmacology*; D039741:Antigens, Dermatophagoides / Q000276:immunology; D001190:Arylsulfonates / Q000494:pharmacology*; D001249:Asthma / Q000276:immunology; D002460:Cell Line; D018925:Chemokines / Q000096:biosynthesis* / Q000235:genetics; D004306:Dose-Response Relationship, Immunologic; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D007371:Interferon-gamma / Q000494:pharmacology; D015847:Interleukin-4 / Q000494:pharmacology; D008213:Lymphocyte Activation / Q000276:immunology; D008297:Male; D012333:RNA, Messenger / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013452:Sulfonium Compounds / Q000494:pharmacology*; D018417:Th1 Cells / Q000276:immunology; D018418:Th2 Cells / Q000187:drug effects* / Q000276:immunology; D013950:Thymus Gland / Q000187:drug effects* / Q000276:immunology; D014373:Tuberculin / Q000276:immunology
D018926:Anti-Allergic Agents; D039741:Antigens, Dermatophagoides; D001190:Arylsulfonates; D018925:Chemokines; D012333:RNA, Messenger; D013452:Sulfonium Compounds; D014373:Tuberculin; D015847:Interleukin-4; D007371:Interferon-gamma; C073028:suplatast tosilate