A rare allele combination of the interleukin-1 gene complex is associated with high interleukin-1 beta plasma levels in healthy individuals

Increases in the plasma levels of the inflammatory cytokines can be detecte d in various infectious and inflammatory diseases, but in healthy individua ls these levels are in most cases low or undetectable, There is now increas ing evidence that genes of the inflammatory cytokines are polymorphic and t he various alleles may differ in their capability to produce the cytokine, We have measured the plasma levels IL-1 beta of 400 healthy blood donors an d correlated these to the genotype (biallelelic base exchanges at the posit ion - 889 of the IL-1 alpha gene, and at the position - 511 of the IL-1 bet a gene and the pentaallelic VNTR in the second intron of the IL-1Ra gene), The median concentration of IL-1 beta was 5.8 pg/ml (upper and lower quarti les 2.2-13.6). The polymorphisms of the IL-1 beta and IL-1 Ra genes did not have any significant influence on the IL-1 beta levels, but the IL-1 alpha 2.2 homozygotes (32/400 blood donors) had significantly elevated levels (m edian 7.0 pg/ml, quartiles 2.2-22.4, one-way ANOVA p < 0.008 as compared to the IL-1 alpha 1.1 homozygotes and p < 0.02 as compared to the IL-1 alpha 1.2 heterozygotes). This effect of IL-1 alpha 2.2 homozygosity was more pro nounced in donors, who also were carriers of the IL-1 beta allele 2, Thus t hese data suggest that this allele combination has a regulatory effect on b asal IL-1 beta production.