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Thorax 2000;55:842-847; doi:10.1136/thorax.55.10.842
Copyright © 2000 BMJ Publishing Group Ltd & British Thoracic Society.
Thorax 2000;55:842-847 ( October )

Reduced production of interleukin 12 by interferon gamma  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)-gamma .
CONCLUSIONS---Pulmonary IL-12 production is lower in asthmatic subjects. This reduction is not the result of generalised hyporesponsiveness to IFN-gamma . 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 gamma


© 2000 by Thorax

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  • Peters-Golden, M. (2004). The Alveolar Macrophage: The Forgotten Cell in Asthma. Am. J. Respir. Cell Mol. Bio. 31: 3-7 [Full Text]  

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