Increased levels of plasma interleukin-6 soluble receptor in patients with essential thrombocythemia.
OBJECTIVE
The pathogenesis of essential thrombocythemia (ET), a disease characterized by megakaryocyte hyperplasia and persistent thrombocytosis, is not completely clarified. Interleukin-6 (IL-6), one of the cytokines related to megakaryocytic development, exerts its effect through binding to a cell surface receptor, IL-6Ra, and a signal transducing unit, gp130. Interestingly, the soluble form of the IL-6Ra, IL-6sR, is an agonist for IL-6 activity. In order to evaluate the possible participation of IL-6sR in ET we measured its levels in 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.


METHODS
Fifty-five patients with ET were evaluated. IL-6sR and IL-6 were measured by an ELISA technique. Mononuclear cells 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 intraplatelet 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.


CONCLUSIONS
Increased plasma 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.
Marta
Rosana
R
Sección Hematología Investigación, Instituto de Investigaciones Médicas Alfredo Lanari, Facultad de Medicina, Universidad de Buenos Aires, Argentina.
Goette
Nora
N
Lev
Paola
P
Heller
Paula
P
Kornblihtt
Laura
L
Vassallú
Patricia
P
Glembotsky
Ana
A
Pirola
Carlos
C
Molinas
Felisa
F
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001792:Blood Platelets / Q000737:chemistry; D002478:Cells, Cultured; D005260:Female; D006801:Humans; D015850:Interleukin-6 / Q000097:blood; D007963:Leukocytes, Mononuclear; D008297:Male; D008875:Middle Aged; D012333:RNA, Messenger / Q000032:analysis; D019947:Receptors, Interleukin-6 / Q000032:analysis* / Q000097:blood / Q000235:genetics; D012995:Solubility; D013920:Thrombocythemia, Essential / Q000097:blood* / Q000209:etiology
D015850:Interleukin-6; D012333:RNA, Messenger; D019947:Receptors, Interleukin-6