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màj 23/07/98 |
Report
by Claire Abbal on the following session :
| Vendredi
13 Février 1988 |
Présentateurs/Speakers
|
Modérateurs
|
Experts
|
16h30-18h00
|
Cytokines Molécules
d'adhésion
|
Ph. Gosset (Lille)
M.
Humbert (Paris)
N.
Frossard (Illkirsh)
Discussion
|
15'
15' 15' 45'
|
K.F.
Chung (Londres)
M.
Petrolani (Paris)
|
M.
Saetta (Padoue, I)
C. Gratziou
(Grèce)
|
Philippe Gosset presented
data about bronchial inflammation in patients with status
asthmaticus, and showed that increased levels of pro- and
anti- inflammatory cytokines as well as neutralizing
soluble receptors were measured in bronchoalveolar
lavages (BAL).
M. Pretolani asked what could mean the concomittant
production of cytokines with opposite effects on
inflammation and wondered wether they are produced by
same cells. Dr Gosset answered that the inflammation
development was accompanied by the production of
inflammatory cytokines like IL-1b or TNFa
and in a second phase the anti-inflammatory
factors appeared to control or limit the inflammatory
reaction. He added that in case of status asthmaticus
these last were not efficient enough.
B. Wallaert suggested that, as there might be a time
factor in the relation pro- and anti- inflammatory
cytokines, it could be of interest to follow up these
patients and to analyze the cytokine content of their BAL
versus time. Have you an idea of the cell source of these
cytokines, from results that you could have obtained by
in situ hybridization or flow cytometry ? asked M.
Pretolani. Pr Gosset answered, it was not possible to
collect bronchial biopsies from patients with that
pathology, for of medical and ethical reasons.
Results communicated by Pr Gosset also highlighted a
strong accumulation of neutrophils and neutrophil
elastase in BAL of patients with status asthmaticus.
|
Dr. Gosset precised that patients included in his study have
been treated with high dose of steroids, it was an evidence that
they were hospitalized in intensive care units. This information
leaded to the following suggestion : a control is to know wether
steroids could be involved in the neutrophil activation. This
activation could come from a combination of mechanical
ventilation and steroid treatment. M Pretolani added that
steroids have been shown to increase survival of neutrophils in
vitro while it induced apoptosis of eosinophils. P Gosset
answered that there is evidence that neutrophils are involved in
severe asthma, as it has been demonstrated in sputum, and it was
underlined that patients presenting another pathology and also
treated by corticosteroids never reach the number of neutrophils
(up to 80% of cells) found in BAL of those with severe asthma.
Marc Humbert presented results on
bronchial expression of pro-eosinophilic cytokines in atopic and
non atopic asthma. Particularly, he showed that IL-5 was highly
expressed in bronchial biopsies of asthmatics, as well as
eotaxin. The chairman K F Chung wondered how these cytokines,
expressed in different cells, could interact to induce
eosinophilia. D Humbert answered mentionning a study from T.
Williams group, published in J. Exp. Med, where in guinea pigs it
has been shown that eotaxin and IL-5 acted synergistically to
induce the activation of eosinophils and their local recruitment.
But K F Chung objected that IL-5 is targetting the bone marrow to
increase the differenciation of eosinophils, and their homing is
under the eotaxin control. M. Humbert agreed with the fact that
IL-5 is critical in the bone marrow, but added that it promotes
survival of eosinophils in inflammed tissues.
K F Chung said that eotaxin was also important in the cellular
adhesion process as it has been shown to up-regulate VLA-4, and
thus increased adhesion of eosinophils to vascular endothelium
via VLA-4/CD11b mechanisms.
According to S. Holgate, in epithelium and in endothelium of
asthmatics the level of numerosous molecules is altered, and that
if picking up some of them to look at their expression and role
is interesting, the real question to ask is why these molecules
are differently regulated. The feeling of M. Humbert on this
point was that, even if the answer could not be clear, genetic
process could probably be involved, but a problem is the lack of
animal's model of asthma. KF Chung added that severe asthma could
be a "disease of transcription factors", as epithelium
expresses activated nucleofactors, and about genetic analysis, he
wondered why not looking at the gene expression in the cells of
airways rather than in blood, to find more specific genes. Noone
answered.
The question of the relation between IL-5, a-chemokines and total IgE level was then
pointed out. M Humbert said that according to his study and
others, IL-5 is up-regulated in asthma irrespective of atopy,
IL-4 is linked to IgE level, IL-5 correlates with disease
severity, and IL-4 and IL-5 do not correlate with each other, so
IL-4 is critical for IgE and atopy and IL-5, CCR-3 and eotaxin
are critical for asthma, but not for IgE. Asthma and atopy are
discriminated in these studies. The next step is to look at the
local production of IgE mRNA in the submucosa in non atopic
patients who have very low levels of serum IgE.
As IL-5 and eotaxin exhibited good correlation with clinical
symptoms of asthma, it was asked if these molecules could
constitute better clinical marker of inflammation than do the
number of eosinophils or the level of ECP. The answer was : if
these cytokines are detectable in the sputum, why not? But to
date they have been detected only in biopsies, not in blood.
The last speaker of this session, Nelly
Frossard, talked about relationship between mast cells and
fibroblasts.
She focused on the SCF, a mast cell growth factor produced by
fibroblasts, and showed that glucocorticoids had a biphasic
effect on SCF from a fibroblast cell line in vitro, reducing its
expression first and then enhancing it. The first question, from
KF Chung, brang N Frossard to precise that fibroblasts studied
were not stimulated and that the effect of steroids could be
different if the SCF was inducible by activation of cells. KF
Chung concluded from the long-term effects of steroids that they
could be nocive. N Frossard argued that steroids benefic effect
is to reduce the number of mast cells. But P Chanez pointed out
that a number of studies on this point were controversial and
some of them have shown that steroids did not have such effects.
As regard of the perspective, N Frossard said that the next step
will consist to look at the SCF expression in bronchial biopsies.
. 
Enfumosa Congrès Conçue et réalisée par: Michel Godard (at) Top
Date de création: 12 Février 1998 -Dernière mise à jour: 23/07/98
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