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The genes of the interleukin-1 (IL-1) complex code for three proteins: IL-1[alpha], IL-1[beta] 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-1[beta] 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-1[beta]/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-1[beta]. We found that the IL-1RA allele 2 (IL1RN*2) is associated with the presence of allele 2 of the IL-1[beta] gene (position -511) and with the absence of allele 2 of the IL-1[beta] 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-1[beta] in vitro. However, IL-1RA allele 2 strongly increased in vitro production of IL-1[beta], regardless of the presence or absence of these alleles. Taken together, these data suggest that the known allelisms in the IL-1[beta] gene are not major regulators of thein vitro IL-1[beta] production, but the IL-1RA allele 2 (or an unknown allele strongly associated with it) has a decisive role.

(C) 1998 Blackwell Science Ltd.