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Recombinant human interleukin-6 induces a rapid and reversible anemia in
cancer patients
J Nieken, NH Mulder, J Buter, E Vellenga, PC Limburg, DA Piers and EG de Vries
Department of Internal Medicine, University Hospital Groningen, The
Netherlands.
Initial studies have shown that recombinant human interleukin-6 (rhIL- 6)
induces anemia. Until now, the pathophysiologic mechanism of this induced
anemia has been unknown. To unravel the underlying mechanism, we examined
15 cancer patients receiving rhIL-6 as an antitumor immunotherapy in a
phase II study. rhIL-6 was administered subcutaneously at 150 micrograms
once daily for 6 consecutive weeks. Various hematologic and biochemical
parameters were measured weekly during rhIL-6 treatment and 4 weeks after
rhIL-6 discontinuation. To determine plasma volume and red blood cell (RBC)
volume, radioisotope dilution assays with labeled autologous RBCs and with
human serum albumin were performed before rhIL-6 administration and on day
8 of rhIL-6 therapy. Hemoglobin levels decreased (mean change +/- SE) 7%
+/- 1.5% within 3 days after the start of rhIL-6 therapy (P < .0001) and
19% +/- 2% at week 4. Levels had normalized at follow-up. The plasma volume
increased 18% +/- 5% during the first week of rhIL-6 administration (P <
.003), whereas RBC volume remained unaffected. The mean RBC corpuscular
volume remained unchanged for 2 weeks and then began to decrease slowly,
reaching its nadir at week 6 (5% +/- 1%; P < .01). Serum iron levels
decreased 65% +/- 12% at week 4 (P < .002) and then returned to initial
baseline values. Erythropoietin levels increased rapidly up to 68% at week
3 (P < .0001) and had normalized 4 weeks after rhIL-6 therapy. Levels of
serum albumin, prealbumin, and transferrin decreased (P < .0001, P <
.003, and P < .0001, respectively), whereas levels of serum amyloid A (P
< .003), C-reactive protein, haptoglobin, and alpha-1-antitrypsin (P
< .0001) increased during rhIL-6 treatment. All levels returned to
pretreatment values after discontinuation of rhIL-6. No alterations in
reticulocyte counts, serum lactic dehydrogenase levels, and bilirubin
levels were observed. A 6-week regimen of subcutaneous rhIL-6 results in a
rapid dilution anemia, caused by an acute and significant increase in
plasma volume and followed by hypoferremia. This anemia is reversible after
the cessation of rhIL-6 treatment.
Volume 86,
Issue 3,
pp. 900-905,
08/01/1995
Copyright © 1995 by The American Society of Hematology
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