Low serum levels of tumor necrosis factor and interleukin-1β in myelodysplastic syndromes responsive to recombinant erythropoietin

Background. Tumor necrosis factor (TNF) and interleukin-1β (IL-1) are two cytokines with erythropoietic inhibitory activity which may be involved in the pathogenesis of some types of anemia that may respond to recombinant erythropoietin (r-EPO). The aim of the present study was to evaluate whether TNF and IL-1 serum levels are related to clinical response in patients with myelodysplastic syndromes (MDS) receiving r-EPO. TNF and IL-1 serum levels were measured by means of immunoenzymatic assays in 26 patients affected by MDS and treated with r-EPO administered subcutaneously at dosages up to 1050 U/kg a week, for at least two months. Four patients (15%) showed a significant response, with an increase of hemoglobin > 2 g/dL and complete suspension of transfusions. Higher mean serum levels of both TNF (54.2 ± 93 vs 4.2 ± 7.9 pg/mL, p <0.001) and IL-1 (114 ± 58.5 vs 36.1 ± 21.7 pg/mL, p <0.001) were measured in MDS patients than in a group of 42 normal controls. However, responders showed significantly lower mean levels of TNF (8.2 ± 9.6 vs 58.5 ± 65.2 pg/MA, p ≤ 0.05) and IL-1 (30 ± 24.8 vs 127.8 ± 51.4 pg/mL, p <0.001) than those of non responders. In terms of absolute values, all responders evidenced undetectable or normal levels of both cytokines. No relationship was found between TNF or IL-1 and values of hemoglobin, serum erythropoietin, ferritin, soluble transferrin receptor or transfusional requirements. MDS patients who respond to r-EPO have lower serum levels of TNF and IL-1 than those who do not respond.