Imbalance production between interleukin-1beta (IL-1beta) and IL-1 receptor antagonist (IL-1Ra) in bronchial asthma.
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.
Mao
X Q
XQ
Experimental Medicine Unit, University of Wales Swansea, Swansea, United Kingdom.
Kawai
M
M
Yamashita
T
T
Enomoto
T
T
Dake
Y
Y
Sasaki
S
S
Kataoka
Y
Y
Fukuzumi
T
T
Endo
K
K
Sano
H
H
Aoki
T
T
Kurimoto
F
F
Adra
C N
CN
Shirakawa
T
T
Hopkin
J M
JM
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*
D007375:Interleukin-1; D017472:Receptors, Interleukin-1