Imbalance production between interleukin-1beta (IL-1beta) and IL-1 receptor antagonist (IL-1Ra) in bronchial asthma.

Abstract

Genes of the IL-1 family encode three different peptides, IL-1alpha, IL-1beta, and IL-1Ra, respectively. IL-1 operates through IL-1RI, and is involved in airway inflammation in asthmatic subjects, whereas IL-1Ra appears to be a specific competitive inhibitor of IL-1. All genes are on chromosome 2q12-21 where genomewide searches have identified linkage for asthma. To test whether variants of IL-1 relate to asthma, we conducted a genetic association study in a Japanese population. We show that the A2 allele of IL1RN (encoding IL-1Ra) associates with nonatopic asthma [OR = 5.71, 95% CI: 1.63-19. 8, Pc = 0.007]. Both atopic and nonatopic asthmatics with the A2 allele had significantly lower serum IL-1Ra levels in both types of asthmatics. Peripheral blood cells from asthmatics with A2 alleles, however, produced as much IL-1 as did those with A1 homozygotes. Since Th1 and Th2 cytokines differentially regulate the ratio between IL-1beta and IL-1Ra, these findings suggest that dysregulation of IL-1beta/IL-1Ra, probably due to interaction between epithelium and immuno-competent cells in the airway, is important in asthma inflammation.

• Authors: X Q Mao, M Kawai, T Yamashita, T Enomoto, Y Dake, S Sasaki, Y Kataoka, T Fukuzumi, K Endo, H Sano, T Aoki, F Kurimoto, C N Adra, T Shirakawa, J M Hopkin
• Journal: Biochemical and biophysical research communications (Biochem Biophys Res Commun) Vol. 276 Issue 2 Pg. 607-12 (Sep 24 2000) ISSN: 0006-291X [Print] United States
• PMID: 11027520 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright 2000 Academic Press.

Chemical References

• Interleukin-1
• Receptors, Interleukin-1

Topics

• Adult
• Asthma (blood, genetics, metabolism)
• Female
• Genetic Testing
• Genotype
• Humans
• Interleukin-1 (blood, genetics, metabolism)
• Male
• Phenotype
• Receptors, Interleukin-1 (antagonists & inhibitors)