Background: The immunosuppressive effects of tacrolimus are mediated by inh
ibition of cytokine production by inflammatory cells. The role of tacrolimu
s on cytokine production and release of chemical mediators in asthma is not
known at present.
Objectives: We compared the effects of tacrolimus on interleukin (IL)-5 and
tumor necrosis factor-alpha (TNF-alpha) production and chemical mediator r
elease from excised human lung tissue with those of steroids.
Methods: Human lung tissue was passively sensitized with serum from atopic
patients then preincubated with tacrolimus (10(-6), 10(-7), 10(-8) M) or de
xamethasone (10(-6) M) for 2 hours. The lung tissue was then exposed to 1.5
mug/mL of mite antigen and then cultured for 48 hours. Culture supernatant
s were collected and IL-5 and TNF-cr levels were measured by ELISA. IL-5 an
d TNF-alpha messenger ribonucleic acid (mRNA) expression was also investiga
ted by reverse transcriptase-polymerase chain reaction. The level of histam
ine and leukotriene E4 was also measured in the culture supernatant. In add
ition, tryptase staining was performed to compare degranulation of mast cel
Results: Antigen stimulation increased histamine and leukotriene release in
the supernatant. Tacrolimus significantly and dose-dependently inhibited t
he release of histamine and leukotriene; dexamethasone did not. The results
of tryptase staining demonstrated that tacrolimus dose-dependently inhibit
ed degranulation of mast cells, whereas dexamethasone did not. Antigen stim
ulation increased TNF-alpha and IL-5 protein production and mRNA expression
. Tacrolimus and dexamethasone significantly inhibited TNF-alpha and IL-5 p
rotein production and mRNA expression.
Conclusions: Our results indicated that tacrolimus is more powerful in inhi
bition of cytokine production and release of chemical mediators than steroi
ds, and suggested that this immunosuppressor drug might be useful for the t
reatment of asthma.