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Effect of recombinant human interleukin-6 (rhIL-6) and rhIL-3 on
hematopoietic regeneration as demonstrated in a nonhuman primate
chemotherapy model
EF Winton, J Srinivasiah, BK Kim, CD Hillyer, EA Strobert, JL Orkin, RB Swenson, HM McClure, LA Myers and R Saral
Emory University School of Medicine, Atlanta, GA.
Using a recently developed hepsulfam-induced pancytopenia model in rhesus
macaques, we have studied the effects of recombinant human interleukin-6
(rhIL-6) and rhIL-3 on marrow regeneration. Control animals were given
hepsulfam (1.5 g/m2 by a single 30-minute intravenous [i.v.] injection, n =
4), while study animals received hepsulfam followed by rhIL-6, rhIL-3, or a
combination of rhIL-6 and rhIL-3 (n = 3 per study group). Each cytokine was
administered by once- daily subcutaneous (SC) injection (15
micrograms/kg/d) for 3 weeks beginning the day after chemotherapy (days 2
through 22). Mean platelet counts in control animals were <
100,000/microL on days 15 through 24, with 50% of the counts <
50,000/microL and two of four animals requiring platelet transfusion. In
the rhIL-6- and rhIL-6/rhIL-3- treated groups, the nadir mean platelet
counts were 164,000 +/- 58,700/microL and 162,300 +/- 23,800/microL,
respectively, and occurred on day 15. Platelet counts in the rhIL-3-treated
group were similar to those in controls. Mean absolute neutrophil counts
(ANCs) < 1,000/microL occurred on days 10 through 29 in control animals,
days 8 through 15 in rhIL-6-treated animals, and days 6 through 8 and 13 in
rhIL-6/rhIL-3-treated animals. The frequency of ANCs < 500/microL was
significantly less in the rhIL-6- and rhIL-6/rhIL-3-treated groups versus
control groups (2.7 +/- 0.6 and 2.0 +/- 1.0 vs 7.0 +/- 1.4 occurrences,
respectively; P < .05). rhIL-3-treated animals had ANCs similar to those
in controls; one animal died with septicemia on day 21. Monkeys receiving
rhIL-6 were significantly more anemic during the cytokine administration
period; however, the anemia resolved by day 24. Coadministration of rhIL-3
and rhIL-6 partially corrected the anemia. The data indicate that rhIL-6
prevents significant thrombocytopenia and shortens the neutropenic period
in this chemotherapy model.
Volume 84,
Issue 1,
pp. 65-73,
07/01/1994
Copyright © 1994 by The American Society of Hematology

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