title: 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.affiliation: Experimental Medicine Unit, University of Wales Swansea, Swansea, United Kingdom.
authors.forename: X Q
authors.initials: XQ
authors.lastname: Mao
authors.forename: M
authors.initials: M
authors.lastname: Kawai
authors.forename: T
authors.initials: T
authors.lastname: Yamashita
authors.forename: T
authors.initials: T
authors.lastname: Enomoto
authors.forename: Y
authors.initials: Y
authors.lastname: Dake
authors.forename: S
authors.initials: S
authors.lastname: Sasaki
authors.forename: Y
authors.initials: Y
authors.lastname: Kataoka
authors.forename: T
authors.initials: T
authors.lastname: Fukuzumi
authors.forename: K
authors.initials: K
authors.lastname: Endo
authors.forename: H
authors.initials: H
authors.lastname: Sano
authors.forename: T
authors.initials: T
authors.lastname: Aoki
authors.forename: F
authors.initials: F
authors.lastname: Kurimoto
authors.forename: C N
authors.initials: CN
authors.lastname: Adra
authors.forename: T
authors.initials: T
authors.lastname: Shirakawa
authors.forename: J M
authors.initials: JM
authors.lastname: Hopkin
mesh_terms: D000328:Adult; D001249:Asthma / Q000097:blood / Q000235:genetics / Q000378:metabolism*; D005260:Female; D005820:Genetic Testing; D005838:Genotype; D006801:Humans; D007375:Interleukin-1 / Q000097:blood / Q000235:genetics / Q000378:metabolism*; D008297:Male; D010641:Phenotype; D017472:Receptors, Interleukin-1 / Q000037:antagonists & inhibitors*
chemical_list: D007375:Interleukin-1; D017472:Receptors, Interleukin-1