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SummaryIncreased levels of interleukin-6 (IL-6) have been reported in patients with a history of venous thromboembolism (VTE); however, prospective studies did not confirm an association between inflammatory markers that are highly correlated with IL-6 and the risk of VTE. It was the aim of our study to investigate the association of IL-6 and its promoter polymorphism (−174) G>C with the risk of spontaneous VTE. IL-6 was measured in 128 patients with deep venous thrombosis (DVT, 70 w / 58 m),105 with pulmonary embolism (PE, 58w/ 47 m) and 122 healthy controls (60 w / 62 m) with a highly sensitive ELISA (Quantikine− HS Human IL-6 Immunoassay, RnDSystems®). The promoter polymorphism was determined by genotyping, allele specific PCR was followed by high resolution gel-electrophoresis. Median concentrations [interquartile ranges] were 2.37 [1.51–3.89] (pg/ ml) in patients with DVT, 2.83 [1.83–4.87] in those with PE and 2.51 [1.71–4.78] in controls (p = 0.6, p = 0.4). Hetero- or homozygous carriers of the C allele (71% in DVT, 67% in PE and 59% among controls) did not have higher IL-6 levels than homozygous carriers of the G allele (median 2.60 vs. 2.59 pg/ml, p = 0.7). In conclusion, we found no association of IL-6 and its promoter polymorphism (−174) G>C with the risk of spontaneous VTE.