Sickle cell disease (SCD) is a chronic inflammatory condition, even in steady state, as indicated by elevated levels of inflammatory cytokines and increased Th17 responses, compared with healthy controls. These inflammatory pathways may be directly regulated by genetic polymorphisms and could be associated to different outcomes of the disease. High levels of a number of different circulating cytokines were found in SCD patients in several studies, and changes in the cytokine balance in SCD patients are an important risk factor for the occurrence of clinical events. Moreover, inter-patient variations in cytokine levels could be attributed to gene polymorphisms. To investigate cytokine polymorphisms and their association with cytokines expression we evaluated the IL4 intron3 VNTR (genotypes 1.1, 1.2, 2.2, 2.3), IL4T590C/T, IL6174G/C and TNFA308A/G polymorphisms and their correlation with TGFB, IL-4, IL-6 and IL-10 expression in steady-state SCD patients. Methods. Fourth-nine patients (24 male and 25 female; 39.8 ± 9.59 years) with SCD and 28 (22 male and 6 female; 35.5 ± 10.2 years) healthy blood donors were evaluated. The polymorphisms were performed by PCR-RFLP analysis described as [individuals (genotype frequencies)] and the expression of TGFB, IL-4, IL-6 and IL-10 by q-PCR expressed as [median (max-min)]. Results. A higher frequency of 1.2, 2.2 and 2.3 genotypes was found in SCD patients compared with normal controls [34(0.69) vs 12 (0.44), P=0.03]; higher expression of IL-4 was found in the ones carrying the 1.1 genotype [0.31 (2.53-0.01) vs 0.05 (0.95-0.0), P=0.047] and although no differences were found in the IL4T590C/T, IL6174G/C and TNFA308A/G polymorphism frequencies, a significantly greater expression of TGFB, IL6 and IL10 was observed in the patients cohort compared to normal individuals [1.55 (9.02-0.0) vs 0.97 (5.46-0.0), P=0.019]; [0.18 (45.45-0.0) vs 0.0 (8.14-0.0), P=0.03] and [0.98 (22.84-0.0) vs 0.0 (9.95-0.0), P Conclusion: A unique distribution of IL-4 genotypes was observed in our cohort of patients and controls, probably related to the miscellaneous ethnic background of our population. The highest prevalence of the IL4intron3 polymorphism in sickle cell patients suggests a less secretory phenotype associated with increased expression of inflammatory cytokines. IL-4 plays an important role in tissue adhesion and inflammation, including induction of adhesion molecules on vascular endothelial cells and could be responsible for a more “inflammatory” phenotype. Despite the small number of patients enrolled, our study brings insights and new data regarding the deregulation in immune system affecting SCD patients and this information must be investigated in larger cohorts, and may help to better characterize individual variations in immune responses and new markers for disease morbidity. Disclosures No relevant conflicts of interest to declare.