Recombinant human interleukin-6 (rhIL-6) is a pluripotent cytokine wit
h proinflammatory, antitumor, and growth factor effects. Clinical inve
stigations of rhIL-6 either alone as immunotherapy or as a colony-stim
ulating factor in conjunction with chemotherapy have shown a dose-depe
ndent, rapid onset, and largely reversible decrease in venous hematocr
it levels. In an effort to determine the mechanism for the rhIL-6-asso
ciated anemia, we measured red blood cell volume serially in patients
receiving rhIL-6 at either 30 mu g/ kg/day as a 120-hour continuous in
travenous infusion (renal cell carcinoma) or 100 mu g/kg/d intravenous
ly over 1 hour for 5 days (melanoma) as part of two separate phase II
trials. Radioisotope dilution assays with Cr-51-labeled autologous red
blood cells and hemolysis screens were performed on day 1 before the
initiation of therapy and on day 5 shortly before the end of therapy.
In the 6 patients studied, the mean decrease in hemoglobin concentrati
on was 1.9 +/- 0.94 g/dL. The mean decrease in the hematocrit level wa
s 6% +/- 2% and the mean increase in total blood volume was 731 +/- 33
7 mL. These changes were explained by a mean decrease in red blood mas
s of 106 +/- 109 mL and a mean increase in plasma volume of 743 +/- 28
9 mL. The decrease in red blood cell mass was largely explained by phl
ebotomy during the hospitalization, but was not statistically signific
ant (paired t-test, P = .06). All other changes were statistically sig
nificant (P < .05). Simple regression analysis indicated that the decr
ease in hematocrit level and increase in plasma volume were related (y
= -1.78 - .0066X; R = -.74). Measurements of lactate dehydrogenase, b
ilirubin, haptoglobin, and reticulocyte counts and serial stool hemocc
ults did not indicate hemolysis or blood loss. We conclude that the an
emia caused by IL-6 is caused by an increase in plasma volume. (C) 199
5 by The American Society of Hematology.