Reduced production of interleukin 12 by interferon
primed
alveolar macrophages from atopic asthmatic subjects
M J Plummeridgea, L Armstronga, M A Birchallb, A B Millara
a Lung Research
Group, University of Bristol, Medical School Unit, Southmead Hospital,
Westbury on Trym, Bristol BS10 5NB, UK, b Department of Otorhinolaryngology
Correspondence to: Dr A Millar email:Ann.Millar{at}bristol.ac.uk
Received 4 February 2000; Returned to authors 6 April 2000; Revised version received 28 June 2000; Accepted for publication 3 July 2000
BACKGROUND
Asthma is
characterised pathologically by an inflammatory pulmonary infiltrate
rich in T helper (Th) 2 cells and eosinophils. Interleukin (IL)-12 is a
heterodimeric cytokine critical for driving the development of
uncommitted Th cells to express a Th 1 phenotype. Reduced pulmonary
production of IL-12 may therefore play a role in the pathogenesis of
asthma by contributing to the pulmonary cytokine imbalance seen in asthma.
METHODS
IL-12 p70
protein levels in bronchoalveolar lavage fluid and p70 protein levels
and IL-12 messenger RNA in alveolar macrophage cultures from normal and
atopic asthmatic subjects were measured.
RESULTS
There was a
significant difference between the mean IL-12 p70 protein level in the
bronchoalveolar lavage fluid from asthmatic subjects (37.5 pg/ml) and
from normal subjects (131 pg/ml, p = 0.04). Alveolar macrophages from
asthmatic subjects produced significantly less IL-12 protein
(30 pg/ml) and messenger RNA than those from normal subjects
(69.5 pg/ml, p<0.005). These differences were not caused by
inhibition of IL-12 production by IL-10 nor to generalised hyporesponsiveness of asthmatic alveolar macrophages from subjects to
the effects of interferon (IFN)-
.
CONCLUSIONS
Pulmonary
IL-12 production is lower in asthmatic subjects. This reduction is not
the result of generalised hyporesponsiveness to IFN-
. Reduced IL-12
levels may contribute to the development of asthmatic pulmonary
inflammation through dysregulation of Th cell development.
Keywords: asthma; alveolar macrophages; interleukin 12; interferon
© 2000 by Thorax
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