Presence of the IL-1RA allele 2 (IL1RN*2) is associated with enhanced IL-1beta production in vitro

Scand J Immunol. 1998 Mar;47(3):195-8. doi: 10.1046/j.1365-3083.1998.00300.x.


The genes of the interleukin-1 (IL-1) complex code for three proteins: IL-1alpha, IL-1beta and the IL-1 receptor antagonist (IL-1RA). Each of these genes is polymorphic and there is increasing evidence that certain alleles are associated with increased susceptibility to a given disease of inflammatory nature. In the IL-1beta gene there are two base-exchange polymorphisms in positions -511 and +3953, and IL-1RA gene has a penta-allelic polymorphic site in intron 2 containing variable numbers of an 86-bp tandem repeat sequence. As the IL-1beta/IL-1RA ratio may be critical in the regulation of inflammation, we examined whether there are allelic associations between these loci (thus suggesting co-ordinate regulation) and whether these have an effect on the in vitro production of IL-1beta. We found that the IL-1RA allele 2 (IL1RN*2) is associated with the presence of allele 2 of the IL-1beta gene (position -511) and with the absence of allele 2 of the IL-1beta gene (position +3953). Mononuclear cells from carriers of allele 2 (position -511) and non-carriers of allele 2 (position +3953) had a slight, but non-significant, elevated capacity to produce IL-1beta in vitro. However, IL-1RA allele 2 strongly increased in vitro production of IL-1beta, regardless of the presence or absence of these alleles. Taken together, these data suggest that the known allelisms in the IL-1beta gene are not major regulators of the in vitro IL-1beta production, but the IL-1RA allele 2 (or an unknown allele strongly associated with it) has a decisive role.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alleles*
  • Blood Donors
  • Cells, Cultured
  • Genotype
  • Humans
  • Interleukin 1 Receptor Antagonist Protein
  • Interleukin-1 / biosynthesis*
  • Interleukin-1 / genetics
  • Leukocytes, Mononuclear / metabolism
  • Sialoglycoproteins / genetics*


  • IL1RN protein, human
  • Interleukin 1 Receptor Antagonist Protein
  • Interleukin-1
  • Sialoglycoproteins