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)-α 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.