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Adoptive immunotherapy with high-dose interleukin-2: kinetics of
circulating progenitors correlate with interleukin-6, granulocyte
colony-stimulating factor level
E Tritarelli, E Rocca, U Testa, G Boccoli, A Camagna, F Calabresi and C Peschle
Department of Hematology and Oncology, Istituto Superiore di Sanita, Rome,
Italy.
Immunotherapy with interleukin-2 (IL-2) and lymphokine-activated killer
(LAK) cells results in significant tumor regression in patients with
advanced cancer. We have investigated the kinetics of circulating erythroid
(BFU-E) and granulocytic-macrophage (CFU-GM) progenitors after IL-2 therapy
in 11 cancer patients, mainly affected by metastatic melanoma and renal
cell carcinoma. Administration of IL-2 from day 1 through day 5 constantly
induced a dramatic decrease of the number of circulating BFU-E and CFU-GM,
which then showed a striking rebound (up to values fourfold and sevenfold
higher, respectively, than the pretherapy levels) on discontinuation of
IL-2, ie, from day 5 through day 10. A similar kinetic pattern was observed
during and after the second cycle of IL-2 administration. 3[H]-thymidine
killing experiments showed that the cycling activity of the progenitors was
virtually unmodified in the rebound phases. To explore the mechanism(s)
underlying this kinetic pattern, we have analyzed the plasma concentration
of several hematopoietic growth factors, including IL-1 beta, IL-3, IL-4,
IL-6, granulocyte-macrophage colony-stimulating factor (GM-CSF), G-CSF, and
erythropoietin (Ep). No modifications in the levels of IL-3, GM-CSF, or
IL-1 beta were observed, whereas a pronounced increase of IL-6 and G-CSF
concentration was monitored, starting at day 3 and peaking at day 5 of
treatment (a parallel, but modest, increase of Ep level was also observed).
The elevation of IL-6 and G-CSF concentration is directly correlated with
and may, at least in part, underlie the subsequent rebound of circulating
hematopoietic progenitors. Furthermore, the increase in IL-4 level observed
at day 10 of therapy may mediate the eosinophilia gradually starting at
this stage of treatment.
Volume 77,
Issue 4,
pp. 741-749,
02/15/1991
Copyright © 1991 by The American Society of Hematology
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