The impact of IL18 gene polymorphisms on mRNA levels and interleukin-18 release by peripheral blood mononuclear cells

Abstract

Introduction: Interleukin-18 (IL-18) is a pleiotropic cytokine playing an important role as a modulator of immune responses, found to play a role in pathogenesis of numerous inflammatory-associated disorders. In the present study a potential association between 7 common single-nucleotide polymorphisms (SNPs) spanning the whole IL18 gene, gene expression and the release of IL-18 from the stimulated peripheral blood mononuclear cells (PBMCs) was investigated. Materials/Methods: PBMCs were isolated from peripheral blood of 29 healthy volunteers, genotyped for the presence of IL18 SNPs: rs1946518: A>C, rs187238: G>C, rs360718: A>C, rs360722: C>T, rs360721: C>G, rs549908: T>G, and rs5744292: A>G. IL-18 concentration and IL18 mRNA levels were investigated after incubation of cells for 48 h with different stimulants (PHA, LPS, and anti-CD3/CD28 antibodies). Results: After treatment with LPS and antibodies IL-18 concentrations were significantly lower in rs1946518AA homozygotes than in C allele carriers. When differences in IL18 mRNA levels between non-stimulated and stimulated cells were analyzed, significantly decreased gene expression was noted in rs1946518 AA homozygotes (as compared with C allele carriers) in samples treated with PHA and LPS. Similar trends were observed in the case of rs187238 SNP; however, the differences reached statistical significance only after PHA treatment. Conclusions: Our study supports the role of rs1946518 (-607A>C) and rs187238 (-137G>C) SNPs as genetic determinants of the observed variability in IL18 expression.