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Imbalances Between Interleukin-1 and Tumor Necrosis Factor Agonists and Antagonists in Stable COPD

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Abstract

Introduction

Interleukin-1 beta (IL-1β) and tumor necrosis factor alpha (TNFα) are potentially important in Chronic Obstructive Pulmonary Disease (COPD), but little is known of the relationships between these cytokines and their antagonists in disease compared with healthy controls. It is unclear if concentrations relate to disease severity. The study aimed to investigate these relationships and to assess the potential activity of each cytokine in the context of their antagonists.

Methods

Plasma cytokines, soluble receptors, and cell counts were measured in patients with stable COPD and age-matched healthy controls (n = 15 for both) daily for 5 days; these mediators were also measured in corresponding sputum samples from the COPD patients.

Results

COPD patients had significantly reduced concentrations of the antagonists, IL-1sRII, and IL-1RA compared with controls. In COPD, IL-1β exceeded its antagonists and correlated significantly with BMI and FEV1, while plasma IL-1RA correlated positively with BMI but negatively with sputum IL-1β, neutrophil, and macrophage counts and smoking history. TNFα antagonists exceeded agonists in both groups and did not correlate with COPD severity.

Conclusions

Endogenous IL-1β antagonists appear reduced in COPD. Furthermore, IL-1β correlated with clinical aspects of disease severity, suggesting that IL-1β may play a critical role in COPD. Given the relevant concentrations and binding affinities, it is likely that TNFα has limited activity in stable COPD.

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Acknowledgements

We wish to thank Diane Griffiths for her help with patient recruitment during this study and AstraZeneca for unrestricted funding for the study. The salary of E Sapey was supported by the West Midlands Chest Fund.

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Authors and Affiliations

  1. Department of Medicine, University of Birmingham, Birmingham, B15 2TT, UK

    Elizabeth Sapey & Ali Ahmad

  2. Department of Respiratory Medicine, University Hospital Birmingham, Birmingham, UK

    Darren Bayley & Robert A. Stockley

  3. Research and Development, AstraZeneca, London, UK

    Paul Newbold, Noel Snell & Paul Rugman

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  1. Elizabeth Sapey
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  2. Ali Ahmad
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Correspondence to Elizabeth Sapey.

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Sapey, E., Ahmad, A., Bayley, D. et al. Imbalances Between Interleukin-1 and Tumor Necrosis Factor Agonists and Antagonists in Stable COPD. J Clin Immunol 29, 508–516 (2009). https://doi.org/10.1007/s10875-009-9286-8

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  • DOI: https://doi.org/10.1007/s10875-009-9286-8

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