Circulating levels of thrombopoietic and inflammatory cytokines in patients with clonal and reactive thrombocytosis

The regulation of megakaryocytopoiesis and thrombopoiesis appears to be und er the control of an array of hematopoietic growth factors. To determine th e relationship between endogenous cytokine levels and circulating platelet counts, we measured the serum levels of both thrombopoietic and inflammator y cytokines in the peripheral brood and bone marrow samples from 70 patient s with clonal thrombocytosis (CT) caused by myeloproliferative disorders, 2 8 patients with reactive thrombocytosis (RT), and 35 normal control subject s, The levels of thrombopoietin (TPO), interleukin-6 (IL-6), soluble IL-6 ( sIL-6) receptor, IL-11, stem cell factor (SCF), IL-3, and IL-8 were determi ned by enzyme-linked immunosorbent assay (ELISA). Platelet counts were sign ificantly higher in both CT and patients with RT (699 +/- 399 x 10(9)/L, P< .001; 642 +/- 200 x 10(9)/L, P<.001; respectively) as compared with the nor mal control subjects (240 +/- 47 x 10(9)/L). The concentrations of cytokine s in the bone marrow correlated well with those in the peripheral blood. Th e endogenous levels of TPO, IL-6, and sIL-6 receptor were significantly hig her in both CT and patients with RT than those in normal control subjects, The median level of IL-6 was significantly higher in patients with RT than in patients with CT (40 pg/mL vs 5 pg/mL; P <.001); however, there was no d etectable difference in TPO and sIL-6 receptor levels between the two group s. Significantly higher levels of SCF and IL-8 were also found in patients with CT as compared with those found in normal control subjects (median 246 0 pg/mL vs 1995 pg/mL, P <.05; 20 ng/mL vs 5 ng/mL, P =.001; respectively). Finally, IL-11 and IL-3 levels were undetectable in most patients with thr ombocytosis. Our results reveal that the endogenous levels of TPO, IL-6, sI L-6 receptor, IL-8,and SCF are elevated in patients with CT or RT. These cy tokines appear to be active mediators involved in the regulation of thrombo poiesis during clonal and reactive thrombocytosis.