M. Hurme et S. Santtila, IL-1 RECEPTOR ANTAGONIST (IL-1RA) PLASMA-LEVELS ARE COORDINATELY REGULATED BY BOTH IL-1RA AND IL-1-BETA GENES, European Journal of Immunology, 28(8), 1998, pp. 2598-2602
The genes in the IL-1 complex code for three proteins, IL-1 alpha, IL-
1 beta and the IL-1 receptor antagonist (IL-1Ra). The severity of a gi
ven infection is influenced by the balance between the levels of IL-1
beta, the major extracellular agonist, and that of IL-1 Ra. In healthy
individuals, IL-1Ra is readily detectable in plasma but IL-1 beta lev
els are usually undetectable. As there are polymorphisms in both of th
ese genes, we have now analyzed whether there are allelic associations
between these loci and whether these would have an influence on plasm
a IL-1Ra levels. In 200 healthy blood donors, the mean plasma IL-1Ra c
oncentration was 681 pg/ml. The IL-1Ra allele 2 (IL1RN2) had a clear
influence on IL-1Ra levels: its carriers had higher levels than the no
n-carriers (745 ng/ml vs. 627 pg/ml, p < 0.05, t-test). As marker alle
les for IL-1 beta we used two biallelic base-exchange polymorphisms (a
t positions -511 and +3953 relative to the transcriptional start site)
. The more rare allele of IL-1 beta -511 (allele 2) was significantly
associated with the presence of IL-1 Ra allele 2, but in the case of t
he IL-1 beta +3953, the more rare allele (allele 2) was less frequent
in the carriers of the IL-1Ra allele 2. These IL-1 beta allelisms did
not have a direct influence on plasma IL-1Ra levels, but the enhancing
effect of IL-1Ra allele 2 on IL-1Ra plasma levels required the presen
ce of the IL-1 beta -511 allele 2 or absence of the IL-1 beta +3953 al
lele 2. Taken together, these results indicate that the IL-1 beta gene
participates in the regulation of IL-1Ra production in vivo and that
the alleles of IL-1 beta and IL-1Ra which demonstrate this cooperative
effect are often associated.