Increased plasmatic IL-6 soluble receptor in patients with essential thrombocythemia

MARTA ROSANA F; GOETTE NORA P; LEV PAOLA R; HELLER PAULA G; KORNBLIHTT LAURA I; VASSALLU PATRICIA S; GLEMBOTSKY ANA C; PIROLA CARLOS J; MOLINAS FELISA C

HAEMATOLOGICA

European Hematology Association

Año: 2004 vol. 89 p. 657 - 663

0390-6078

Background and objectives The pathogenesis of essential thrombocythemia (ET), a disease characterized by megekaryocyte hyperplasia and persistent thrombocytosis, is not completely clarified. Interleukin- 6 (IL-6), one of the cytokines related to megakaryocytic development, exerts its effects through binding to a cell surface receptor IL-6Ra, and a signal transducing unit, gp130. Interestingly, the soluble form of IL-6Ra, IL-6sR, is an agonist for IL-6 activity. In order to evaluate the possible participation of IL-6R in ET, we measured its levels on plasma, platelets and in the supernatant of a mononuclear cell culture. We also evaluated IL-6R on leukocyte membrane and IL-6R/IL-6sR mRNA expression in mononuclear cells. Design and methods Fifty-five patients with ET were evaluated. IL-6sR and IL-6 were measured by an ELISA technique. Mononuclear cell were cultured for 48 hr and IL-6sR released into the supernatant was measured. IL-6R on leukocyte surfaces was evaluated by flow cytometry. IL-6R and IL-6sR mRNA levels were assessed by semi-quantitative reverse transcription polymerase chain reaction. Results Plasma IL-6sR levels were increased while platelet levels were low in untreated ET patients. Plasma levels decreased during treatment. Non-stimulated mononuclear cells from ET patients released greater amounts of IL-6sR than did cells from normal controls in 48-hour culture. No abnormality was found in IL-6R or IL-6sR mRNA expression by mononuclear ET cells. IL-6R on leukocyte surfaces was normal. Interpretations and Conclusions Increased IL-6sR levels might have a role in the abnormal megakaryocytic proliferation seen in ET patients, while platelets and mononuclear cells could be the source of the above-mentioned high levels of plasma IL-6sR.