A. Tsukadaira et al., Theophylline inhibits TNF-alpha-induced CD4 expression on human eosinophils and CD4+eosinophil migration, INT A AL IM, 125(4), 2001, pp. 335-343
Background: Increasing evidence regarding asthma suggests that CD4+ cells a
re preferentially recruited to sites of bronchial inflammation. Interleukin
(IL)-16 has been reported as playing an important role in the accumulation
of CD4+ cells. We have shown that the CD4 molecule is expressed on normal
human eosinophils by tumor (TNF)-alpha stimulation. Methods: We evaluated t
he effects of theophylline, KF19514 [a selective phosphodiesterase (PDE) IV
inhibitor] and dexamethasone on CD4 expression on eosinophils and eosinoph
il migration in response to IL-16, a natural soluble ligand of the CD4 mole
cule. Results: The maximum eosinophil migration was observed when eosinophi
ls were cultured with TNF-alpha at 10 ng/ml for 18 h and the concentration
of IL-16 was 10 pg/ml. CD4+ eosinophil migration in response to IL-16 was m
ostly, if not fully, chemokinetic and this migration was significantly inhi
bited by Fab of anti-CD4 monoclonal antibody. Theophylline (10(-4)-10(-3) M
), KF19514 (10(-7)-10(-6) M) and dexamethasone (10(-8)-10(-6) M) significan
tly inhibited CD4 expression on eosinophils induced by TNF-alpha. Theophyll
ine (10(-3) M) and KF19514 (10(-6) M) inhibited CD4+ eosinophil migratory r
esponses induced by IL-16, but 10(-6) M dexamethasone did not. Theophylline
and KF19514 augmented the intracellular adenosine-3 ' ,5 ' -cyclic monopho
sphate (cAMP) concentration in eosinophils, suggesting modulation by cAMP o
f CD4 expression and eosinophil migration. Conclusions: These data suggest
that TNF-alpha -induced CD4+ eosinophils may contribute to eosinophil migra
tory responses induced by IL-16. Theophylline and selective PDE IV inhibito
r may prevent airway inflammation by downregulating CD4 expression on eosin
ophils and inhibiting eosinophil migration through CD4 and IL-16 necrosis f
actor interaction. Copyright (C) 2001 S. Karger AG, Basel.