EFFECTS OF INTERLEUKIN-6 ON MOBILIZATION OF PRIMITIVE HEMATOPOIETIC-CELLS INTO THE CIRCULATION

Twenty-seven patients with advanced adenocarcinoma were studied. Group s of three patients received interleukin-6 (IL-6) in doses ranging fro m 0.5 to 20 mu g/kg by daily subcutaneous injection on days 1-7 and 22 -49. Four patients received IL-6 2.5 mu g/kg/d with GM-CSF 5 mu g/kg/d and three patients received IL-6 2.5 mu g/kg/d with IL-3 5 mu g/kg/d. Circulating platelet numbers increased 1.65-fold during IL-6 treatmen t, in a dose-dependent fashion (P = 0.01). This increase is inferior t o that expected from laboratory studies. No significant change in tota l WBC was seen after IL-6 alone. After treatment with IL-6, significan t increases in numbers of circulating mononuclear cells (2.2-fold, P = 0.006) and GM-CFC numbers (3.2-fold, P = 0.01) were seen, but there w ere no changes in circulating megakaryocyte-CPC numbers. In contrast, after treatment with IL-6 and GM-CSF, larger increases in both circula ting GM-CFC (20-fold, P = 0.04) and megakaryocyte-CFC numbers (Is-fold , P = 0.03) were seen. Increases in brood progenitors after treatment with IL-6 and IL-3 did not achieve statistical significance. The abili ty of peripheral blood mononuclear cells to generate and sustain long- term haemopoiesis in vitro was similar in IL-6-treated patients to tha t in untreated control subjects. No significant changes in the inciden ce of bone marrow progenitors or their cycling status (assessed by thy midine suicide) were seen. These data suggest that IL-6 alone will not be clinically useful to mobilize blood progenitor cells in cancer pat ients.