Reduced production of interleukin 12 by interferon γ primed alveolar macrophages from atopic asthmatic subjects
- aLung Research Group, University of Bristol, Medical School Unit, Southmead Hospital, Westbury on Trym, Bristol BS10 5NB, UK, bDepartment of Otorhinolaryngology
- Dr A Millar email:Ann.Millar{at}bristol.ac.uk
- Received 4 February 2000
- Revision requested 6 April 2000
- Revised 28 June 2000
- Accepted 3 July 2000
Abstract
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)-γ.
CONCLUSIONS Pulmonary IL-12 production is lower in asthmatic subjects. This reduction is not the result of generalised hyporesponsiveness to IFN-γ. Reduced IL-12 levels may contribute to the development of asthmatic pulmonary inflammation through dysregulation of Th cell development.
