Xq. Mao et al., Imbalance production between interleukin-1 beta (IL-1 beta) and IL-1 receptor antagonist (IL-1Ra) in bronchial asthma, BIOC BIOP R, 276(2), 2000, pp. 607-612
Citations number
32
Categorie Soggetti
Biochemistry & Biophysics
Journal title
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
Genes of the IL-I family encode three different peptides, IL-1 alpha, IL-1
beta, and IL-1Ra, respectively. IL-1 operates through IL-1RI, and is involv
ed in airway inflammation in asthmatic subjects, whereas IL-1Ra appears to
be a specific competitive inhibitor of IL-I. All genes are on chromosome 2q
12-21 where genomewide searches have identified linkage for asthma. To test
whether variants of IL-1 relate to asthma, we conducted a genetic associat
ion study in a Japanese population. We show that the A2 allele of IL1RN (en
coding 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 ha
d significantly lower serum IL-1Ra levels in both types of asthmatics. Peri
pheral blood cells from asthmatics with A2 alleles, however, produced as mu
ch IL-1 as did those with Al homozygotes. Since Th1 and Th2 cytokines diffe
rentially regulate the ratio between IL-1 beta and IL-1Ra, these findings s
uggest that dysregulation of IL-1 beta/IL-1Ra, probably due to interaction
between epithelium and immune-competent cells in the airway, is important i
n asthma inflammation. (C) 2000 Academic Press.