Effects of interleukin-1 on hematopoietic progenitors: evidence of
stimulatory and inhibitory activities in a primate model
C Gasparetto, J Laver, M Abboud, A Gillio, C Smith, RJ O'Reilly and MA Moore
Bone Marrow Transplantation Service, Memorial Sloan-Kettering Cancer
Center, New York.
The effects of recombinant human interleukin-1 rhIL-1 beta (rhIL-1b) on
hematopoietic recovery following chemotherapy in a primate model were
investigated. Cynomolgus monkeys received 1 microgram/kg/day rhIL-1b
intravenously for 2, 7, and 14 days following 5-Fluorouracil (5-FU)
treatment (75 mg/kg x 2 days). Compared with controls, a significantly
shortened time to achieve an absolute neutrophil (ANC) count over
500/microL was observed in animals receiving 2- and 7-day courses of
rhIL-1b (17 v 30 days), while animals receiving a 14-day course of rhIL- 1b
achieved an ANC over 500/microL by 23 days. Concomitantly, a marked
increase in granulocyte-macrophage colonies (CFU-GM) was observed at 14
days following 5-FU in animals receiving 2- and 7-day rhIL-1b courses. In
animals receiving a 14-day rhIL-1b course, a significant increase in CFU-GM
relative to control was not seen until 21 days post 5-FU. Utilizing a
serum-free colony assay system, a 50% inhibition of normal marrow CFU-GM
growth was observed with the addition of sera obtained on day 9 post 5-FU
from animals receiving rhIL-1b for 14 days. Sera obtained at any time from
animals receiving 2- and 7-day rhIL-1b treatment did not show any growth
inhibition. Addition of antibodies to TNFa to the coculture assay abrogated
the CFU-GM growth inhibition. TNFa levels in sera with the inhibitory
activity was relatively high (918 pg/mL). Our data indicate that rhIL-1b
enhances hematopoietic recovery following 5-FU if administered for short
periods of time (less than 7 days), whereas prolonged administration has a
counterproductive effect that is due in part to the induction of TNFa
production.
Volume 74,
Issue 2,
pp. 547-550,
08/01/1989
Copyright © 1989 by The American Society of Hematology
