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Pimecrolimus induces apoptosis of mast cells in a murine model of cutaneous mastocytosis.
[cutaneous mastocytosis]
Cutaneous
mastocytosis
(
CM
)
is
a
common
type
of
mastocytosis
.
Current
treatment
of
CM
is
generally
symptomatic
.
Pimecrolimus
has
been
demonstrated
as
an
effective
anti-
inflammatory
drug
for
the
treatment
of
inflammatory
skin
diseases
,
but
whether
it
treats
CM
remains
unknown
.
The
murine
model
of
CM
was
induced
by
subcutaneous
injection
of
100
μg
/
kg
recombinant
murine
stem
cell
factor
(
rmSCF
)
for
a
total
of
17
days
in
Balb
/
c
mice
.
Beginning
on
the
8
th
day
,
treatment
with
pimecrolimus
1
%
cream
or
vehicle
was
performed
topically
and
daily
for
10
days
.
The
clinical
signs
of
CM
were
scored
,
and
pathological
analysis
was
performed
with
toluidine
blue
staining
and
hematoxylin
and
eosin
staining
.
The
in
situ
apoptotic
mast
cells
(
MCs
)
were
studied
by
terminal
deoxynucleotidyl
transferase-mediated
dUTP
nick
-end
labeling
assay
.
The
cutaneous
histamine
level
was
measured
by
ELISA
.
In
the
rmSCF-treated
mice
,
the
clinical
signs
of
CM
,
including
erythema
,
wheal
after
rubbing
lesion
skins
,
and
increased
thickness
of
skin
,
were
obvious
compared
to
control
mice
,
and
were
reduced
after
pimecrolimus
treatment
.
The
numbers
of
cutaneous
MCs
and
neutrophils
were
significantly
greater
in
mice
with
CM
than
in
control
mice
,
and
pimecrolimus
treatment
decreased
the
numbers
of
MCs
but
not
neutrophils
.
Extensive
apoptosis
of
cutaneous
MCs
was
observed
in
pimecrolimus-treated
mice
.
The
cutaneous
histamine
level
was
elevated
in
the
mice
with
CM
compared
with
healthy
controls
,
and
was
lowered
after
treatment
with
pimecrolimus
.
Pimecrolimus
effectively
treats
CM
by
reducing
the
density
of
cutaneous
MCs
and
the
subsequent
histamine
production
through
inducing
MCs
apoptosis
.
Diseases
Validation
Diseases presenting
"erythema"
symptom
acute rheumatic fever
cowden syndrome
cutaneous mastocytosis
epidermolysis bullosa simplex
erythropoietic protoporphyria
familial mediterranean fever
harlequin ichthyosis
inclusion body myositis
kindler syndrome
lamellar ichthyosis
legionellosis
liposarcoma
malignant atrophic papulosis
neuralgic amyotrophy
omenn syndrome
pyomyositis
thoracic outlet syndrome
This symptom has already been validated