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Ex vivo PBMC cytokine profile in familial Mediterranean fever patients: Involvement of IL-1β, IL-1α and Th17-associated cytokines and decrease of Th1 and Th2 cytokines.
[familial mediterranean fever]
In
order
to
clarify
the
inflammatory
mechanism
underlying
familial
Mediterranean
fever
(
FMF
)
,
we
aimed
to
evaluate
the
ex
vivo
cytokine
profile
of
FMF
patients
during
acute
attacks
and
attack-free
periods
,
and
compare
it
with
that
of
healthy
controls
.
The
study
included
34
FMF
patients
,
of
whom
9
were
studied
during
attack
and
remission
and
24
healthy
controls
.
Cytokine
levels
were
evaluated
by
Luminex
technology
in
serum
and
supernatants
of
PBMC
(
Peripheral
Blood
Mononuclear
Cells
)
cultures
with
and
without
24
h
stimulation
of
monocytes
by
LPS
and
T
lymphocytes
by
anti-
CD
3
/
CD
28
beads
.
Levels
of
IL
-
6
and
TNF
-α
were
higher
in
unstimulated
and
LPS-stimulated
PBMC
supernatants
of
FMF
patients
in
crises
compared
to
controls
.
In
response
to
LPS
stimulation
,
higher
levels
of
IL
-
1
β
and
IL
-
1
α
were
found
in
PBMC
supernatants
of
patients
during
crises
compared
to
those
in
remission
and
to
controls
.
IFN-γ
and
IL
-
4
levels
were
the
lowest
in
unstimulated
and
anti-
CD
3
/
CD
28
stimulated
PBMCs
supernatants
of
patients
during
crises
compared
to
remission
and
controls
.
The
Th
17
cytokines
IL
-
17
and
IL
-
22
were
respectively
higher
in
anti-
CD
3
/
CD
28
stimulated
PBMC
supernatants
of
FMF
patients
during
and
between
crises
compared
to
controls
.
Amongst
cytokines
tested
in
serum
,
only
IL
-
6
and
TNF
α
were
enhanced
in
FMF
patients
.
The
ex
vivo
study
represents
an
interesting
approach
to
evaluate
cytokines
'
involvement
in
FMF
.
Our
results
suggest
an
ongoing
subclinical
inflammation
and
define
an
elevated
inflammatory
cytokine
signature
,
distinctly
for
M
694
V
homozygous
patients
.
The
absence
of
spontaneous
IL
-
1
β
release
by
PBMCs
reflects
no
constitutive
activation
of
the
inflammasome
in
FMF
physiopathology
.
Diseases
Validation
Diseases presenting
"inflammatory mechanism"
symptom
familial mediterranean fever
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