Objective: To investigate the association of alleles in interleukin-1(IL-1) family genes with IL-1alpha, IL-1beta, IL-1ra production as well as mRNA expression and the outcome of sepsis.
Methods: Sixty septic patients and equal number of healthy volunteers were enrolled in this study. Monocytes of healthy volunteers segregated by Ficoll were stimulated by lipopolysaccharide (LPS) in vitro. IL-1alpha, IL-1beta and IL-1ra mRNA expressions were semi-quantitatively analyzed with reverse transcription-polymerase chain reaction (RT-PCR). Cytokine production was determined with enzyme linked immunoadsorbent assay(ELISA). Alleles in IL-1A (intron 6, VNTR), IL-1B (-511, RLFP) and IL-1RN (intron 2, VNTR) were screened in all cases.
Results: The number of individuals carrying allele of IL-1RN2 was significantly greater in septic patients than that in healthy volunteers. Mortality in septic patients with IL-1RN2, compared with IL-1RN1, was markedly higher. Notably, IL-1ra production as well as mRNA expression of monocytes challenged with LPS was significantly higher in IL-1RN2 allele than in IL-1RN1 carriers. However, there was no difference in the coded gene expression between alleles of IL-1A1 and IL-1A2, also between IL-1B1 and IL-1B2.
Conclusion: IL-1RN2 allele induces high IL-1ra expression and is closely with the outcome of patients in sepsis. It could be one of high risk genetic factors in septic patients.