title: Low serum levels of tumor necrosis factor and interleukin-1 beta in myelodysplastic syndromes responsive to recombinant erythropoietin.
abstract: BACKGROUND. Tumor necrosis factor (TNF) and interleukin-1 beta (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/mL, 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.
authors.affiliation: Division of Hematology, IRCCS Casa Sollievo della Sofferenza Hospital, Italy.
authors.forename: P
authors.initials: P
authors.lastname: Musto
authors.forename: R
authors.initials: R
authors.lastname: Matera
authors.forename: M M
authors.initials: MM
authors.lastname: Minervini
authors.forename: C
authors.initials: C
authors.lastname: Checchia-de Ambrosio
authors.forename: C
authors.initials: C
authors.lastname: Bodenizza
authors.forename: A
authors.initials: A
authors.lastname: Falcone
authors.forename: M
authors.initials: M
authors.lastname: Carotenuto
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D004921:Erythropoietin / Q000627:therapeutic use*; D006801:Humans; D007375:Interleukin-1 / Q000097:blood*; D008875:Middle Aged; D009190:Myelodysplastic Syndromes / Q000097:blood* / Q000188:drug therapy*; D011994:Recombinant Proteins / Q000627:therapeutic use; D016896:Treatment Outcome; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*
chemical_list: D007375:Interleukin-1; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; D004921:Erythropoietin