A. Kaser et al., Interleukin-6 stimulates thrombopoiesis through thrombopoietin: role in inflammatory thrombocytosis, BLOOD, 98(9), 2001, pp. 2720-2725
Baseline platelet production is dependent on thrombopoietin (TPO). TPO is c
onstitutively produced and primarily regulated by receptor-mediated uptake
by platelets. Inflammatory thrombocytosis is thought to be related to incre
ased interleukin-6 (IL-6) levels. To address whether IL-6 might act through
TPO to increase platelet counts, TPO was neutralized in vivo in C57BL/10 m
ice treated with IL-6, and hepatic TPO mRNA expression and TPO plasma level
s were studied. Transcriptional regulation of TPO mRNA was studied in the h
epatoblastoma cell line HepG2. Furthermore, TPO plasma levels were determin
ed in IL-6-treated cancer patients. It is shown that IL-6-induced thrombocy
tosis in C57BL/10 mice is accompanied by enhanced hepatic TPO mRNA expressi
on and elevated TPO plasma levels. Administration of IL-6 to cancer patient
s results in a corresponding increase in TPO plasma levels. IL-6 enhances T
PO mRNA transcription in HepG2 cells. IL-6-induced thrombocytosis can be ab
rogated by neutralization of TPO, suggesting that IL-6 induces thrombocytos
is through TPO. A novel pathway of TPO regulation by the Inflammatory media
tor IL-6 is proposed, indicating that the number of platelets by themselves
might not be the sole determinant of circulating TPO levels and thus of th
rombopoiesis. This regulatory pathway might be of relevance for the underst
anding of reactive thrombocytosis. (C) 2001 by The American Society of Hema
tology.