EFFECTS OF INTERLEUKIN-6 ADMINISTRATION ON PLATELETS AND HEMATOPOIETIC PROGENITOR CELLS IN PERIPHERAL-BLOOD

Platelet numbers and circulating haemopoietic progenitor cells were ex amined in 12 patients with advanced malignancies who were receiving re combinant human interleukin-6 (rhIL-6) as part of an investigation of its thrombopoietic effects. Patients received recombinant glycosylated IL-6 by daily subcutaneous injection for 7 consecutive days in doses of 1, 3 or 10 mu g/kg/day. Platelet numbers increased reaching a peak on days 12-15 with a mean on day 15 of 198.1% of pre-treatment values. This was accompanied by a significant fall in the mean platelet volum e (mean decrease of 10.6%, P = 0.0044). No significant correlation was seen between the IL-6 dose and the change in platelet number. No sign ificant differences were observed between pre- and post-treatment leve ls of circulating erythroid burst-forming units (E-BFU) and granulocyt e macrophage colony-forming units (GM-CFU) but a small significant inc rease was seen in circulating primitive progenitor cells measured in a plastic-adherent (P Delta) assay (P = 0.025). As positive controls, a group of patients treated with cyclophosphamide/G-CSF showed signific ant increases in GM-CFU (P = 0.018), E-BFU (P = 0.018) and P Delta pro genitors (P = 0.028). These data suggest that the thrombopoietic effec ts of IL-6 are mediated at a relatively late stage via effects on mega karyocyte differentiation, with a relatively small effect on circulati ng haemopoietic progenitors. (C) 1996 Academic Press Limited