A dysbalanced immune response is thought to account for a substantial part of the morbidity and mortality after severe trauma. The cytokine interleukin-10 (IL-10) suppresses the transcription of proinflammatory cytokines, mainly in macrophages and monocytes. The objectives of this prospective study in a level I trauma center in Germany were to examine the distribution of IL-10 promoter polymorphisms in a cohort of severely injured patients, to measure IL-10 cytokine levels and relate these to the genotype, and to identify associations of IL-10 polymorphisms with the incidence of severe multiple organ dysfunction syndrome (MODS). The genotypes of polymorphisms -592 and -1082 were determined by polymerase chain reaction (PCR) and restriction cleavage with Rsa 1 or Mnl I, respectively. We analyzed 119 severely injured trauma patients [mean Injury Severity Score (ISS) 38.0 +/- 13.2]. The frequency of the -1082A allele was 0.542, and that of the -592C allele was 0.807. IL-10 polymorphisms were not significantly associated with mean systemic IL-10 cytokine levels 6, 12, and 18 h after admission to the ICU. Carriers of the genotype -592AC had significantly higher overall MOD scores than non-AC carriers (P = 0.018; P(corr) = 0.036). The genotypes of the IL-10 SNP -1082 were not significantly associated with MOD scores. A multivariate Cox hazard regression analysis including important factors of the patients' anatomic and physiological trauma impact revealed only the shock index, the severity of the head injury, and the IL-10 -592 genotype AC as significant independent risk factors for the development of MODS. In this multivariate analysis, carriers of the genotype -592AC displayed a 3.3-fold increase in the relative risk of developing a MODS (P = 0.008, hazard ratio 3.29, 95% CI 1.36-7.97). Our data suggest a possible link between the AC genotype of the -592 single nucleotide polymorphism and significantly higher mean MOD scores. The AC genotype was associated in multivariate analysis with a higher relative risk of MODS in multiply injured patients. Further investigations in larger cohorts need to focus on the potential diagnostic and therapeutic options of this SNP.