The aim of this analysis was to evaluate the effects of the presence of the IL-1RA gene polymorphism and H. pylori infection on markers of a systemic inflammatory response taking into account virulence markers of this infection. Serum concentrations of interleukin (IL)-6, IL-8, and tumour-necrosis factor (TNF)-alpha of 479 occasional blood donors were not statistically significantly higher in subjects having antibodies against H. pylori, or more specifically against CagA and VacA, and being homozygous for the pro-inflammatory IL-1RN*2 allele compared to others after adjustment for covariates. The findings suggest that the possible pro-inflammatory effect of the IL-1RN*2 allele in combination with H. pylori infection is limited to the mucosal level.