Læknablaðið : fylgirit - 01.08.2002, Blaðsíða 26

ABSTRACTS / 21 ST NORDIC CONGRESS OF ALLERGOLOGY
A GLIMPSE INTO ONGOING RESEARCH IN
ALLERGY AND IMMUNOLOGY IN ICELAND
In this short compendium Icelandic investigators were asked to
give a brief description of their ongoing research in the field of
allergy and immunology. The topics covered are lectures that will
be presented at the meeting.
R 1 - Inflammatory Responses in Respiratory Syncytial
Virus Infection in Infants; Cytokines, Chemokines
and Eosinophil Cationic Protein
Kristjánsson S
Respiratory Syncytial Virus (RSV) is the leading cause of respira-
tory tract infection during infancy. Early childhood RSV infection
has been considered to be a risk factor for developing bronchial
asthma. Cytotoxic T cells are required for virus clearance, but Th2
cells have been implicated in enhanced pathology following RSV
infection. Lung eosinphilia has been associated with a local
reduction in IFN-g production and increased IL-4 production.
Recently we finished the following pilot study. Seventeen
children < 18 months of age with a RSV infection (mean age 3,3
months) were enrolled. RSV infection was confirmed by culture and
immunofluorescence of nasal secretion. Urine was sampled before
12.00 am. The children were seen 3 weeks, 3 months and 2.5 years
after the RSV infection. Skin Prick Test (SPT) for 10 different
allergens was performed
Compared to the initial values U-EPX was slightly elevated
(p=0.07) in the RSV group at the 3 month control (131 vs. 192
mg/mmol creatinine). At the 3 month visit U-EPX in the RSV group
was significantly increased (p=007) compared to the age matched
controls (192 vs. 101 mg/mmol creatinine).
The increased U-EPX values at 3 months after the RSV
infection compared to the controls and also the slightly increased U-
EPX values at that time indicate that the RSV infection causes
activation of eosinophils and probably leads to a Th2 type
inflammation in the majority of the children. However these effects
were not seen at the visit 2.5 years after the RSV infection and
wheezing was not correlated to U-EPX.
The following project has been ongoing the last 2.5 years.
Children with diagnosed RSV infection are being followed until
they are at least 7 years of age. The first results are presented here.
We measured the levels of these cytokines in relation to eotaxin
and eosinophil production of the Eosinophil Cationic Protein in
nasal secretion (N-ECP). ECP was also measured in serum (S-
ECP). Thirty-nine infants < 7 months of age with a RSV infection
(mean age 3 months) were enrolled in the study. RSV infection was
confirmed by culture and immunofluorescence of nasal secretion.
Fifty healthy infants in the same age group with no prior infection
(outside the RSV season) were included as controls.
IL-4, IFN-y and eotaxin in nasal secretions were measured with
sandwich ELISA (R&D Systems, Oxon, UK) and ECP with
UniCap (Pharmacia &Upjohn, Uppsala, Sweden).
There was a significant statistical difference between the RSV
and control groups in levels of IL-4 (0.79 vs. 0.31 pg/mL), (p=0,008)
and IFN-g (0.55 vs. 0.18 pg/mL), (p=0,021). N-ECP levels were
increased in the RSV group (p<0.001) compared to the control
group (378,6 vs. 54,3 pg/L), but S-ECP levels were comparable (3.9
vs. 5.0 pg/L). In the RSV group there was a significant correlation
between IL-4 and N-ECP (R=0.60, p<0.001) and a negative
correlation between lFN--y and N-ECP (R=-0.39, p=0.015). There
was a disparity in the levels of IL-4 and IFN-y in the RSV group
(R=-0.22, p=0.182) as well as in the control group (R=-0.076,
p=0.598). The
IL-4/IFN-g ratios were similar in the RSV group and control
group (1.4 and 1.7). A negative correlation was found between IL-4
and eotaxin (R=-0.48, p=0.002).
In the RSV group eotaxin was significantly higher in infants > 3
months of age compared to infants < 3 months of age (37.8 vs. 13.5
pg/mL, p=0.003). The reverse was true for IL-4 which was primarily
found in infants < 3 months of age (1.1 vs. 0.3 pg/ml, p=0,049).
Increased IL-4 in in nasal secretion in the RSV group compared
to healthy controls as well as a good correlation between IL-4 and
N-ECP levels in RSV infected infants strongly indicates a relative
increase of local production of Th2 cytokines in the RSV group.
R 2 - Genetic factors separating different asthma
phenotypes
Björnsdóttir US
In collaboration with deCode Genetics, we have been using gene
array technology to separate different asthma phenotypes.
1. Atopic vs nonatopic asthma
Atopy and asthma often coincide, however immunopathology,
cellular, molecular and genetic mechanisms may be different.
We used gene array technology to examine whether different
gene expression profiles can separate atopy and asthma. Asthma
phenotype and severity was assessed by medical history, physical
examination, methacholine challenge tests and PFT values. Atopy
was verified by skin prick testing. Patients were classified into three
groups in addition to controls: atopics (allergic rhinitis) without
asthma or with only mild exercise induced asthma, allergic rhinitis
with moderate asthma and nonatopics with moderate asthma. Total
RNA was extracted from peripheral blood mononuclear cells
treated with the inflammatory cytokines IL-1(3 and TNFa. RNA
expression was examined using Affymetrix Hu95A chips, each
recognising over 12600 genes. Expression profiles were analysed by
comparing the mean change of signal intensity in cytokine
stimulated vs not stimulated peripheral blood mononuclear cells in
the 4 different phenotypes.
Certain proinflammatory genes discriminated atopic from
nonatopic subjects, irrespective of asthma (p < 0.05). These included
IL-10, STAT-1 and several IFN related cytokines. Another group of
genes separated asthmatic subjects from those with only allergic
rhinitis p < 0.05). These included IL-2R, IL-8, IL-6, TIMP and NFk(3.
We have thus found that multiple genes known to play an im-
portant role in the regulation and action of inflammatory responses
were differentially expressed between the three study groups:
subjects with allergic rhinitis without asthma or with only exercise
induced symptoms, allergic rhinitis with moderate asthma and
nonatopic subjects with moderate asthma.
26 Læknablaðið/Fylgirit 46 2002/88