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Interleukin-18 is a proinflammatory cytokine, which strongly induces IFN-γ production. We have cloned the human IL-18 promoter and screened for possible polymorphisms. Three single nucleotide polymorphisms were detected in the promoter and two polymorphisms in the 5′-nontranslated region of the gene. Three combinations of these polymorphisms were observed in the Swedish population. All IL-18 promoter alleles were found to have clear promoter activity when inserted into a luciferase reporter vector. There were no significant differences in promoter activity between alleles without stimulation, but after stimulation with PMA/ionomicin one of the alleles had clearly lower activity than the other (P<0.01). Measurement of IL-18 and IFN-γ production in 48 multiple sclerosis patients by RT-PCR showed slightly higher expression of IL-18 in individuals homozygous for the most frequent haplotype. Two IL-18 …