Reduced production of interleukin 12 by interferon γ primed alveolar macrophages from atopic asthmatic subjects

M. J. Plummeridge, L. Armstrong, M. A. Birchall, A. B. Millar

Research output: Contribution to journalArticle

29 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)842-847
Number of pages6
JournalThorax
Volume55
Issue number10
DOIs
StatePublished - 2000
Externally publishedYes

Keywords

  • Alveolar macrophages
  • Asthma
  • Interferon γ
  • Interleukin 12

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine

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