We measured serum levels of thrombopoietin (TPO), interleukin (IL)-11, and
IL-6 in 90 different samples from 67 pediatric patients with thrombocytopen
ia (TP). The cytokine levels were determined by enzyme-linked immunosorbent
assays (ELISA), and the biological activity of TPO was measured using a ce
ll line transfected with human c-mpl. In patients with impaired megakaryocy
topoiesis, as found in diseases such as aplastic anemia, amegakaryocytic TP
, or TP with absent radii, we found TPO levels which were highly elevated c
ompared with normal values (mean = 261 AU/ml, n = 52, vs. 22 AU/ml in healt
hy controls). In contrast, patients suffering from idiopathic thrombocytope
nic purpura (mean = 16 AU/ml, n = 31) or platelet function defects (mean =
23 AU/ml, n = 7) demonstrated normal TPO levels. The biological activity te
sted in the bioassay correlated well with the ELISA data. However, sera of
some patients with amegakaryocytic TP demonstrated a remarkably higher biol
ogical activity of TPO than expected from the ELISA data. Within the differ
ent groups there was no correlation between platelet counts and TPO levels.
Only 27% of all samples had elevated levels of IL-11 (mean = 450 pg/ml, n
= 20). Elevated IL-6 serum levels were detected in only 13% of all samples
analyzed (mean = 42 pg/ml, n = 12). We conclude that megakaryocytopoiesis i
s regulated mainly by TPO, that it is dependent on the platelet and the meg
akaryocytic mass, and that IL-11 plays an additional role in supporting the
platelet production. IL-6 does not appear to be up-regulated in children w
ith thrombocytopenia.