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 language | English (US) |
|---|---|
| Pages (from-to) | 842-847 |
| Number of pages | 6 |
| Journal | Thorax |
| Volume | 55 |
| Issue number | 10 |
| DOIs | |
| State | Published - 2000 |
| Externally published | Yes |
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Keywords
- Alveolar macrophages
- Asthma
- Interferon γ
- Interleukin 12
ASJC Scopus subject areas
- Pulmonary and Respiratory Medicine
Cite this
Reduced production of interleukin 12 by interferon γ primed alveolar macrophages from atopic asthmatic subjects. / Plummeridge, M. J.; Armstrong, L.; Birchall, M. A.; Millar, A. B.
In: Thorax, Vol. 55, No. 10, 2000, p. 842-847.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Reduced production of interleukin 12 by interferon γ primed alveolar macrophages from atopic asthmatic subjects
AU - Plummeridge, M. J.
AU - Armstrong, L.
AU - Birchall, M. A.
AU - Millar, A. B.
PY - 2000
Y1 - 2000
N2 - 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.
AB - 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.
KW - Alveolar macrophages
KW - Asthma
KW - Interferon γ
KW - Interleukin 12
UR - http://www.scopus.com/inward/record.url?scp=0033806816&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0033806816&partnerID=8YFLogxK
U2 - 10.1136/thorax.55.10.842
DO - 10.1136/thorax.55.10.842
M3 - Article
C2 - 10992536
AN - SCOPUS:0033806816
VL - 55
SP - 842
EP - 847
JO - Thorax
JF - Thorax
SN - 0040-6376
IS - 10
ER -