Ebastine inhibits T cell migration, production of Th2-type cytokines and proinflammatory cytokines.
BACKGROUND
Cytokine imbalance and cellular migration to inflammatory sites are critical components of allergic diseases. Redirecting cytokine imbalance and inhibiting cell migration therefore represent important therapeutic strategies for the treatment of these disorders.


OBJECTIVE
To study the in vitro effect of ebastine, a novel non-sedating H1 receptor antagonist, on cytokine secretion and migration of activated T cells, as well as production of pro-inflammatory cytokines by macrophages.


METHODS
Peripheral T cells obtained from healthy volunteers were cultured in wells coated with the combination of anti-CD3 monoclonal antibody (mAb) and anti-CD26 mAb, anti-CD3 mAb and anti-CD28 mAb, or anti-CD3 mAb with PMA, in the presence or absence of ebastine. T cell proliferation and the production of cytokines were measured by [3H]thymidine incorporation assay and ELISA, respectively. In addition, transendothelial migration of T cells and production of pro-inflammatory cytokines by macrophages were examined.


RESULTS
Ebastine inhibited T cell proliferation and the production of IL-4, IL-5, IL-6, and TNF-alpha by T cells under each co-stimulatory condition tested, whereas it exhibited no effect on the production of IL-2 or IFN-gamma. In addition, T cell migration and the production of such pro-inflammatory cytokines as TNF-alpha and IL-6 by macrophages were inhibited by ebastine.


CONCLUSIONS
These results indicate that ebastine has a specific inhibitory effect on Th2-type cytokine production. Moreover, ebastine inhibited T cell migration and pro-inflammatory cytokine production by T cells and macrophages, suggesting that ebastine might be useful for the treatment of T cell-mediated allergic inflammatory disorders, including asthma, atopic dermatitis, and Th2-type autoimmune diseases.
Nori
M
M
Division of Clinical Immunology, Advanced Clinical Research Center, Institute of Medical Science, University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo, Japan.
Iwata
S
S
Munakata
Y
Y
Kobayashi
H
H
Kobayashi
S
S
Umezawa
Y
Y
Hosono
O
O
Kawasaki
H
H
Dang
N H
NH
Tanaka
H
H
Shiohara
T
T
Morimoto
C
C
D015703:Antigens, CD / Q000378:metabolism; D002090:Butyrophenones / Q000494:pharmacology*; D002455:Cell Division / Q000187:drug effects / Q000276:immunology; D002465:Cell Movement / Q000187:drug effects / Q000276:immunology; D002478:Cells, Cultured; D016207:Cytokines / Q000096:biosynthesis*; D004306:Dose-Response Relationship, Immunologic; D004727:Endothelium / Q000276:immunology; D039563:Histamine H1 Antagonists, Non-Sedating / Q000494:pharmacology*; D006801:Humans; D007665:Ketotifen / Q000494:pharmacology; D008213:Lymphocyte Activation / Q000187:drug effects / Q000276:immunology; D008264:Macrophages / Q000187:drug effects / Q000276:immunology; D010880:Piperidines / Q000494:pharmacology*; D016176:T-Lymphocyte Subsets / Q000187:drug effects* / Q000276:immunology; D018417:Th1 Cells / Q000276:immunology; D018418:Th2 Cells / Q000276:immunology
D015703:Antigens, CD; D002090:Butyrophenones; D016207:Cytokines; D039563:Histamine H1 Antagonists, Non-Sedating; D010880:Piperidines; C058249:ebastine; D007665:Ketotifen