Annual General Meeting of the Irish Thoracic Society - IJMS | Irish ...

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SESSION FOUR ONE
ANNUAL MEETING OF THE IRISH THORACIC SOCIETY • 11 - 12 November 2005 • WESTWOOD HOUSE HOTEL, GALWAY
ANNUAL MEETING OF THE IRISH THORACIC SOCIETY • 11 - 12 November 2005 • WESTWOOD HOUSE HOTEL, GALWAY
SESSION
4SESSION FOUR ONE
4.4 4.6 The role of IL-17 in inflammation and remodelling in the
post-transplant airway
4.5 Mast cells and obstructive airways disease 4.7
Introduction
Obliterative Bronchiolitis (OB) is the main cause
of premature allograft failure following lung
transplantation. It’s characterised by airway
neutrophilia, epithelial injury and progressive
fibroproliferative obliteration of small airways.
Airway lymphocytosis is well described in the
lung allograft, particularly during acute rejection
episodes, but potential mechanisms linking this early
inflammation to chronic neutrophilic inflammation
and airway remodelling aren’t well understood.
The lymphocyte-derived cytokine interleukin (IL)-17
has been postulated to play a major role in airway
neutrophilic inflammatory conditions.
Aims
To characterise airway expression of IL-17 in lung
allografts and assess the effects of IL-17 on airway
epithelium with specific reference to neutrophilic
inflammation and remodelling.
Methods
Transbronchial biopsies from lung allografts with
airway inflammation were stained for IL-17 and
the degree of immunostaining in the epithelium
and lamina propria quantified. Confluent primary
bronchial epithelial cell cultures (PBECs) were
established from bronchial brushings of stable
lung allografts (n=10). PBECs were subsequently coincubated
with IL-17 and the resulting levels of IL-8,
IL-6, GCSF, GM-CSF, VEGF, MMP-2 and MMP-9 cell
supernatant protein measured.
Conclusions
Our results suggest IL-17 as a potential mechanistic
link between acute lung allograft rejection,
neutrophil recruitment, airway remodelling and
subsequent progression to OB.
DM Murphy, 1
IA Forrest, 1 C Ward, 1
PA Corris, 1 G Pritchard, 1
D Jones, 2 AJ Fisher, 1
JJ Egan, 3 TE Cawston, 2
JL Lordan 1
1. The Applied
Immunobiology
and Transplantation
Research Group and
Results
Our data demonstrate variable IL-17 immunostaining
of the airway epithelium and mononuclear cell
infiltrate of transbronchial biopsies obtained from
lung transplant recipients. PBEC stimulation with
IL-17 caused significantly raised levels of IL-8, IL-
6, GCSF, GM-CSF and VEGF from baseline. Matrix
metalloproteinase (MMP)-2 and -9 protein levels
were not affected.
2. The Faculty of
Medical Sciences,
The University of
Newcastle-upon-
Tyne
3. The Musculoskeletal
Research Group, The
Faculty of Medical
Sciences, The Irish
Lung Transplant
Programme, The
Mater Hospital,
Dublin
This work was
supported by ERS and
MRC fellowships and
Newcastle-upon-Tyne
Special Trustees.
Viral infection and cytokine responses in exacerbations
of COPD
Introduction
In COPD exacerbations can be triggered by viral
and bacterial infections. Real-time PCR allows
faster and more accurate detection of respiratory
viral infections and assessment of cytokine mRNA
responses. We studied patients with COPD when
stable and during exacerbations to determine the
role of viral infection and airway inflammation.
Method
Patients were recruited with 24 hours of hospital
admission for a COPD exacerbation (AECOPD).
Patients with stable COPD who had no change in
treatment or symptoms over the previous eight
weeks were also recruited (SCOPD). Sputum, nasal
and throat swab specimens were obtained and
screened for respiratory viruses using nested PCR.
Real-time PCR was used to measure mRNA cytokine
responses. Ribosomal RNA (18s rRNA) was employed
as a housekeeping gene. Supernatant from sputum
specimens was analysed for corresponding protein
concentrations of cytokines using the BioPlex system.
All mRNA levels are adjusted for 18s rRNA and
expressed as copies /ml of sputum (c/ml).
Results
One hundred and thirty six patients were recruited
during an acute exacerbation and 68 when stable.
Mean (±SD) age of each group was 70 yrs (± 9) and
66 yrs (± 9) respectively. FEV 1
(% predicted) was as
follows; AECOPD 0.84 ± 0.5 (39%), SCOPD 1.00 ± 0.5
(48%). Smoking history AECOPD 48 ± 39 and SCOPD
42 ± 26 pack years. A respiratory virus was detected
in 50 (37%) AECOPD and in 8 (12%) SCOPD patients (p
< 0.001). TNF-α mRNA levels were higher in AECOPD
(1392 c/ml) than SCOPD (139 c/ml) patients. IL-6 and
IL-8 mRNA was also significantly increased during
AECOPD (219c/ml, 38429 c/ml,) in comparison to
stable patients (27 c/ml, 4071 c/ml p < 0.005). GRO-α
and GM-CSF mRNA levels were increased during
exacerbations (p < 0.005). Expression of growth
factors TGF-β1 and TGF-β2 were also increased in
AECOPD. Corresponding protein concentrations of
IL-6, TNF-α, Interferon-γ and IL-4 were raised during
exacerbations (p < 0.005). TGF-β1 and TNF-α mRNA
levels were higher during those exacerbations in
which a virus was not isolated.
Conclusions
Patients with AECOPD have an increased airway
inflammatory response when compared to the stable
patients. The expression of some cytokine targets are
modulated by respiratory viral infection.
Increased levels of cysteinyl and metalloproteases
mediated by a TH 1 response in COPD patients
TE McManus, 1,2
AM Marley, 1
F De Courcey, 3
N Baxter, 1 SN Christie, 2
HJ O’Neill, 2 JS Elborn, 3,4
PV Coyle, 2 JC Kidney 1
1. Dept of Respiratory
Medicine, Mater
Hospital
2. Regional Virus
Laboratory, Royal
Victoria Hospital
3. Respiratory Research
Group, Institute of
Clinical Science
4. Dept of Respiratory
Medicine, Belfast
City Hospital
Introduction
A few studies have suggested that there are
increased numbers of mast cells in the airways of
patients with COPD. It is thought that they may play
a role in mucous secretion and fibroblast activation.
We looked for evidence of increased mast cell
number in airway biopsies of patients with COPD
and Alpha-1 Antitrypsin deficiency.
Method
Bronchoscopy was performed on six subjects
with COPD, four subjects with Alpha-1 Antitrypsin
deficiency and four normal non-smoking controls. Up
to six biopsies were taken from the subcarinae of the
second to the fourth divisions of the bronchial tree.
Samples were embedded in a GMA resin and stained
immunohistochimically using an antibody to mast
cell tryptase. Positive cells in the submucosa
were expressed per high powered (HP) field at 40x
magnification.
Results
There were more mast cells in the samples from
subjects with COPD compared to normal controls
(1.2 cells / HP field versus 0.73) but this did not reach
statistical significance, (p=0.16). Interestingly there
was a significantly greater number of mast cells seen
in the samples from the individuals with Alpha-1
antitrypsin deficiency compared to controls (2.42
versus 0.73, p