Association of Single Nucleotide Polymorphisms in the IL-18 Gene with Production of IL-18 Protein by Mononuclear Cells from Healthy Donors

IL-18 has proinflammatory effects and participates in both innate and adaptive cellular and humoral immunity. A number of SNPs that influence IL-18 production are found in the gene promoter region. We investigated the association of SNPs in the IL-18 promoter at −607 and −137 with the level of IL-18 protein production by PBMC from healthy donors from Southwestern Siberia. The genetic distribution of these SNPs in the promoter site was established by PCR. IL-18 protein production was determined by ELISA. Our results showed that PBMC from donors carrying allele 137C have lower levels of both spontaneous and LPS-stimulated IL-18 production. In contrast, PBMC from donors carrying allele 607A showed significant increases in spontaneous and stimulated IL-18 production compared to wild type. Our study suggests that the SNPs −607 and −137 in the promoter region of the IL-18 gene influence the level of IL-18 protein production by PBMC from healthy donors in Southwestern Siberia

ТОКСИЧЕСКИЙ ЭПИДЕРМАЛЬНЫЙ НЕКРОЛИЗ (СИНДРОМ ЛАЙЕЛЛА)

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IL–18 AND IMMUNITY

Abstract. Interleukin–18 is one of the main cytokines, inducing production of IFNg. It is the important factor of anti–infectious and anti–tumor immunity. The review represent molecular–genetic and biochemical characteristics of IL–18. The data about producers, the structure of the receptor and of IL–18 binding protein, as well as signal transduction in the cell are considered. Besides that, the main immune effects of IL–18 are discussed. (Med. Immunol., 2005, vol.7, № 4, pp 355–364

IN VITRO STIMULATION OF ANTITUMOR CYTOTOXIC ACTIVITY OF MONONUCLEAR CELLS FROM COLORECTAL CANCER PATIENTS

Abstract. In present study, we investigated the in vitro ability of autologous dendritic cells loaded with tumor lysate antigens to stimulate cytotoxic and secretory activity of effector cells from patients with colorectal cancer. To this purpose, we generated antigen-primed dendritic cells (DS) derived from adherent fraction of peripheral blood mononuclear cells (PBMSc) obtained from patients with colorectal cancer. The DCs were then cocultured with non-adherent mononuclear cells, either in presence of IL-12 and IL-18, or without cytokines. The modulation efficiency was assessed as cytotoxic activity of mononuclear cells towards autologous tumor cells, production of IFNγ, IL-2, IL-4 and the number of perforin-, granzyme B-containing cells. We have demonstrated the ability of dendritic cells to stimulate the in vitro antitumor cytotoxic and secretory activity of effector cells in culture. A combination of dendritic cells with IL-12 and IL-18 is shown to enhance their effects in the mononuclear cells culture, as evidenced by increased percentage of dead autologous tumor cells, higher numbers of perforin(+), granzyme B(+) lymphocytes, and increased production of IFNγ, IL-2 increased