The role of IL-10 receptors in aberrant homeostatic control of TNF-α in idiopathic pulmonary fibrosis (IPF)

H. A. Whittington, A. B. Millar (Westbury-on-Trym, United Kingdom)

Source: Annual Congress 2002 - Interstitial lung disease
Session: Interstitial lung disease
Session type: Assembly Symposium
Number: 3753
Disease area: Interstitial lung diseases

Congress or journal article abstract

Abstract

We have previously shown that alveolar macrophages (AM) of IPF patients exhibit elevated levels of bioactive TNF-α in comparison to normal controls. Additionally, there is only a 2-fold increase in IL-10 protein relative to a 5-fold increase in IL-10 mRNA suggesting that the level of IL-10 produced is unable to maintain the homeostatic regulation of TNF-α in IPF. We are currently examining the role of the IL-10 receptor (IL-10R) in IPF. Altered levels of IL-10R or aberrant signalling may be linked to altered IL-10 levels in IPF. The IL-10R complex is composed of two subunits, IL-10R1 and IL-10R2. The level of IL-10R1 and IL-10R2 mRNA was determined by semi-quantitative RT-PCR of total RNA from AM of IPF (n=7) patients and normal (n=5) controls. AM were isolated by adherence from bronchoalveolar lavage fluid and cultured in vitro +/- 10μg/ml lipopolysaccharide (LPS). PCR products were quantified by densitometry as OD units/mm2. The results are expressed as the median ratio of
IL-10R/GAPDH.

UNSTIMULATEDLPS STIMULATED
Normal IL-10R10.7810.754
IPF IL-10R1 0.587 0.592
Normal IL-10R2 1.098 1.045
IPF IL-10R2 1.038 1.072


The level of IL-10R1 mRNA is lower in IPF patients than in normal controls but there is no difference in the level of IL-10R2 mRNA. We are currently examining the level of IL-10R protein by flow cytometry and alterations in signalling. This work is supported by the British Lung Foundation.


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Citations should be made in the following way:
H. A. Whittington, A. B. Millar (Westbury-on-Trym, United Kingdom). The role of IL-10 receptors in aberrant homeostatic control of TNF-α in idiopathic pulmonary fibrosis (IPF). Eur Respir J 2002; 20: Suppl. 38, 3753

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