Genetic variability in the IL1RN gene and the balance between interleukin (IL)-1 receptor agonist and IL-1β in idiopathic pulmonary fibrosis
Open Access
- 10 August 2011
- journal article
- Published by Oxford University Press (OUP) in Clinical and Experimental Immunology
- Vol. 166 (3), 346-351
- https://doi.org/10.1111/j.1365-2249.2011.04468.x
Abstract
Idiopathic pulmonary fibrosis (IPF) is a rapidly progressive interstitial lung disease of unknown aetiology. Interleukin (IL)-1β plays an important role in inflammation and has been associated with fibrotic remodelling. We investigated the balance between IL-1β and IL-1 receptor antagonist (IL-1Ra) in bronchoalveolar lavage fluid (BALF) and serum as well as the influence of genetic variability in the IL1B and IL1RN gene on disease susceptibility and cytokine levels. In 77 IPF patients and 349 healthy controls, single nucleotide polymorphisms (SNPs) in the IL1RN and IL1B genes were determined. Serum and BALF IL-1Ra and IL-1β levels were measured using a multiplex suspension bead array system and were correlated with genotypes. Both in serum and BALF a significantly decreased IL-1Ra/IL-1β ratio was found in IPF patients compared to healthy controls. In the IL1RN gene, one SNP was associated with both the susceptibility to IPF and reduced IL-1Ra/IL-1β ratios in BALF. Our results show that genetic variability in the IL1RN gene may play a role in the pathogenesis of IPF and that this role may be more important than thought until recently. The imbalance between IL-1Ra and IL-1β might contribute to a proinflammatory and pro-fibrotic environment in their lungs.Keywords
This publication has 28 references indexed in Scilit:
- Imbalance between interleukin-1 agonists and antagonists: relationship to severity of inflammatory bowel diseaseClinical and Experimental Immunology, 2004
- Cytokine gene polymorphisms in idiopathic pulmonary fibrosisInternal Medicine Journal, 2004
- Functional correlates of the interleukin-1 receptor antagonist gene polymorphism in the colonic mucosa in ulcerative colitisGenes & Immunity, 2004
- Inflammatory Mechanisms Are Not a Minor Component of the Pathogenesis of Idiopathic Pulmonary FibrosisAmerican Journal of Respiratory and Critical Care Medicine, 2002
- Inflammatory Mechanisms Are a Minor Component of the Pathogenesis of Idiopathic Pulmonary FibrosisAmerican Journal of Respiratory and Critical Care Medicine, 2002
- Interleukin-1 Gene Cluster Polymorphisms in Sarcoidosis and Idiopathic Pulmonary FibrosisAmerican Journal of Respiratory and Critical Care Medicine, 2002
- Histopathologic Variability in Usual and Nonspecific Interstitial PneumoniasAmerican Journal of Respiratory and Critical Care Medicine, 2001
- Circulating proinflammatory cytokines (IL-1β, TNF-α, and IL-6) and IL-1 receptor antagonist (IL-1Ra) in fulminant hepatic failure and acute hepatitisClinical and Experimental Immunology, 1994
- Interleukin 1 receptor antagonist (IL-1ra) prevents or cures pulmonary fibrosis elicited in mice by bleomycin or silicaCytokine, 1993
- Interleukin-1 Receptor AntagonistAdvances in Immunology, 1993